Breast/Soft Tissue|Articles in Press

Impact of de-escalating systemic therapy guided by 21-gene assay on locoregional recurrence after partial-breast irradiation



      Partial-breast irradiation (PBI) has been performed as alternative to whole-breast irradiation (WBI) in breast-conserving therapy (BCT). Recently, the 21-gene recurrence score (RS) was introduced to determine the adjuvant therapy for estrogen receptor (ER)-positive, and human epidermal growth factor receptor 2 (HER2)-negative diseases. However, the impact of RS-based systemic therapy on locoregional recurrence (LRR) following BCT with PBI remains uninvestigated.


      Patients with ER-positive, HER2-negative, and node-negative breast cancer who underwent BCT with PBI were examined during May 2012–March 2022. In addition to immunohistochemistry (IHC), RS was available to decide on adjuvant therapy.


      In total, 431 patients were evaluated with a median followup of 48.6 months. The 4-year LRR-free survival rates were 97.3% and 96.4% in the IHC and RS cohorts, respectively (p = 0.50). Ki67 of >20% was significantly associated with LRR in the multivariate analysis (HR 4.39, p < 0.05). For patients with Ki67 > 20%, 29 of 71 (40.8%) and 46 of 59 (78.0%) patients received only endocrine therapy in the IHC and RS cohorts, respectively (p < 0.0001). For patients with Ki67 >20% who received only endocrine therapy, the 4-year LRR-free survival rates were 91.8% in the IHC cohort and 94.6% in the RS cohort (p = 0.29)


      Although the introduction of RS increased the number of patients receiving endocrine therapy alone for Ki67 >20% of disease by two times, the LRR-free survival after BCT with PBI could be maintained. However, further studies from multiple institutions with longer followup data are required.


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        • Fisher B
        • Anderson S
        • Bryant J
        • et al.
        Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
        N Engl J Med. 2002; 347: 1233-1241
        • Veronesi U
        • Cascinelli N
        • Mariani L
        • et al.
        Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer.
        N Engl J Med. 2002; 347: 1227-1232
        • Shah C
        • Al-Hilli Z
        • Vicini F
        Advances in breast cancer radiotherapy: implications for current and future practice.
        JCO Oncol Pract. 2021; 17: 697-706
        • Polgar C
        • Van Limbergen E
        • Pötter R
        • et al.
        Patient selection for accelerated partial breast irradiation after breast-conserving surgery: recommendations of the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group.
        Int J Radiat Oncol. 2010; 78: S243
        • Nguyen PL
        • Taghian AG
        • Katz MS
        • et al.
        Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy.
        J Clin Oncol. 2008; 26: 2373-2378
        • Voduc KD
        • Cheang MCU
        • Tyldesley S
        • et al.
        Breast cancer subtypes and the risk of local and regional relapse.
        J Clin Oncol. 2010; 28: 1684-1691
        • Lowery AJ
        • Kell MR
        • Glynn RW
        • et al.
        Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype.
        Breast Cancer Res Treat. 2012; 133: 831-841
        • Orecchia R
        • Leonardi MC
        Partial breast irradiation: targeting volume or breast molecular subtypes?.
        Breast. 2013; 22: S137-S140
        • 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: 3885-3891
        • Smith BD
        • Arthur DW
        • Buchholz TA
        • et al.
        Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO).
        Int J Radiat Oncol Biol Phys. 2009; 74: 987-1001
        • Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
        Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
        Lancet. 2005; 365: 1687-1717
        • Poortmans PMP
        • Arenas M
        • Livi L
        Breast. 2017; 31: 295-302
        • Gao JJ
        • Swain SM
        Luminal A breast cancer and molecular assays: a review.
        Oncologist. 2018; 23: 556-565
        • Goldhirsch A
        • Wood WC
        • Coates AS
        • et al.
        Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011.
        Ann Oncol. 2011; 22: 1736-1747
        • Goldhirsch A
        • Winer EP
        • Coates AS
        • et al.
        Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013.
        Ann Oncol. 2013; 24: 2206-2223
        • Burstein HJ
        • Curigliano G
        • Thürlimann B
        • et al.
        Customizing local and systemic therapies for women with early breast cancer: the St. Gallen international consensus guidelines for treatment of early breast cancer 2021.
        Ann Oncol. 2021; 32: 1216-1235
        • Gnant M
        • Steger GG
        Fighting overtreatment in adjuvant breast cancer therapy.
        Lancet. 2009; 374: 2029-2030
        • Sparano JA
        • Gray RJ
        • Makower DF
        • et al.
        Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer.
        N Engl J Med. 2018; 379: 111-121
        • Thibodeau S
        • Voutsadakis IA
        The Oncotype Dx assay in ER-positive, HER2-negative breast cancer patients: a real life experience from a single cancer center.
        Eur J Breast Heal. 2019; 15: 163-170
        • Sato K
        • Shimo T
        • Fuchikami H
        • et al.
        Catheter-based delineation of lumpectomy cavity for accurate target definition in partial-breast irradiation with multicatheter interstitial brachytherapy.
        J Contemp Brachytherapy. 2019; 11: 108-115
        • Sato K
        • Fuchikami H
        • Takeda N
        • et al.
        Moving incision for covert breast-conserving surgery may prevent early wound complications in brachytherapy-based partial-breast irradiation.
        Brachytherapy. 2019; 18: 645-650
        • Sato K
        • Fuchikami H
        • Takeda N
        • et al.
        Efficacy of single-plane implant technique in partial breast brachytherapy in small-breasted patients.
        Int J Radiat Oncol Biol Phys. 2020; 106: 830-837
        • Jones S
        • Holmes FA
        • O'Shaughnessy J
        • et al.
        Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of us oncology research trial 9735.
        J Clin Oncol. 2009; 27: 1177-1183
        • Budd GT
        • Barlow WE
        • Moore HCF
        • et al.
        SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer.
        J Clin Oncol. 2015; 33: 58-64
        • Perera F
        • Yu E
        • Engel J
        • et al.
        Patterns of breast recurrence in a pilot study of brachytherapy confined to the lumpectomy site for early breast cancer with six years’ minimum follow-up.
        Int J Radiat Oncol Biol Phys. 2003; 57: 1239-1246
        • Paik S
        • Tang G
        • Shak S
        • et al.
        Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
        J Clin Oncol. 2006; 24: 3726-3734
        • Naghavi M
        Europe PMC funders group the global burden of cancer 2013.
        JAMA Oncol. 2015; 1: 505-527
        • Kummerow KL
        • Du L
        • Penson DF
        • et al.
        Nationwide trends in mastectomy for early-stage breast cancer.
        JAMA Surg. 2015; 150: 9-16
        • De Boniface J
        • Szulkin R
        • Johansson ALV
        Survival after breast conservation vs mastectomy adjusted for comorbidity and socioeconomic status: a Swedish national 6-year follow-up of 48986 women.
        JAMA Surg. 2021; 156: 628-637
        • Early Breast Cancer Trialists’ Collaborative Group
        Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials.
        Lancet. 2000; 355: 1757-1770
        • Jagsi R
        • Griffith KA
        • Vicini F
        • et al.
        Identifying patients whose symptoms are underrecognized during treatment with breast radiotherapy.
        JAMA Oncol. 2022; 8: 887-894
        • Hughes KS
        • Schnaper LA
        • Bellon JR
        • et al.
        Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.
        J Clin Oncol. 2013; 31: 2382-2387
        • Kunkler IH
        • Williams LJ
        • Jack WJL
        • et al.
        Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.
        Lancet Oncol. 2015; 16: 266-273
        • Blamey RW
        • Bates T
        • Chetty U
        • et al.
        Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: british Association of Surgical Oncology (BASO) II trial.
        Eur J Cancer. 2013; 49: 2294-2302
      1. Whelan TJ LUMINA: a prospective trial omitting radiotherapy (RT) following breast conserving surgery (BCS) in T1N0 luminal A breast cancer (BC). 2022;9:2022. doi:10.1200/JCO.2022.40.17

        • 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: 2155-2164
        • 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: 2165-2172
        • 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: 4175-4183
        • Strnad V
        • Ott OJ
        • Hildebrandt G
        • et al.
        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. 2016; 387: 229-238
        • Polgár C
        • Fodor J
        • Major T
        • et al.
        Breast-conserving therapy with partial or whole breast irradiation: ten-year results of the Budapest randomized trial.
        Radiother Oncol. 2013; 108: 197-202
        • Hannoun-Levi JM
        • Chamorey E
        • Boulahssass R
        • et al.
        Endocrine therapy with accelerated partial breast irradiation or exclusive ultra-accelerated partial breast irradiation for women aged ≥ 60 years with Early-stage breast cancer (EPOPE): the rationale for a GEC-ESTRO randomized phase III-controlled trial.
        Clin Transl Radiat Oncol. 2021; 29: 1-8
        • Botteri E
        • Bagnardi V
        • Rotmensz N
        • et al.
        Analysis of local regional recurrences in breast cancer after conservative surgery.
        Ann Oncol. 2009; 21: 723-728
        • Jobsen J
        • Van Der Palen J
        • Riemersma S
        • et al.
        Pattern of ipsilateral breast tumor recurrence after breast-conserving therapy.
        Int J Radiat Oncol Biol Phys. 2014; 89: 1006-1014
        • Correa C
        • Harris EE
        • Leonardi MC
        • et al.
        Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement.
        Pract Radiat Oncol. 2017; 7: 73-79
        • Anderson B
        • Arthur D
        • Hannoun-Levi JM
        • et al.
        Partial breast irradiation: an updated consensus statement from the American brachytherapy society.
        Brachytherapy. 2022; 21: 726-747