The modern generation of trials evaluating the role of adjuvant radiation have turned to genomic profiling as a further risk stratification tool. The LUMINA trial by Whelan and colleagues, published in the New England Journal of Medicine , applied Ki67 testing to identify those with luminal A disease and evaluated locoregional outcomes with breast-conserving surgery and endocrine therapy alone. This article was reviewed at the Canadian Association of General Surgeons' "Evidence-Based Reviews in Surgery" webinar series. Here, we present the Evidence-Based Reviews in Surgery panel's methodologic review and clinical commentary. The LUMINA study demonstrated very low rates of local recurrence in low-risk patients with luminal A biologic subtype treated with breast-conserving surgery and endocrine therapy alone without radiation. Although the LUMINA study was rigorously designed and executed, there are significant pragmatic limitations to the implementation of the proposed approach using their protocol. We advocate that there is no "one-size-fits-all" approach to early estrogen receptor + breast cancer. The choice of treatment strategy should strongly consider patient goals and preferences, with the need for incorporation of quality of life and patient-reported endpoints into future studies evaluating this population to help guide these nuanced decisions.
References
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.
Jagsi R, Griffith KA, Vicini F, et al. Toward improving patients’ experiences of acute toxicity from breast radiotherapy: insights from the analysis of patient-reported outcomes in a large multicenter cohort. J Clin Oncol 2020;38:4019–4029.
Batenburg MCT, Mink van der Molen DR, van der Leij F, et al. Patient-reported symptoms of late toxicity in patients with breast cancer treated with hypofractionated radiation therapy and the association with quality of life. Int J Radiat Oncol Biol Phys 2023;115:1181–1191.
Fisher B, Bryant J, Dignam JJ, et al. National Surgical Adjuvant Breast and Bowel Project: tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol 2002;20:4141–4149.
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.
Sauerbrei W, Bastert G, Bojar H, et al. Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients: an update based on 10 years’ follow-up. German Breast Cancer Study Group. J Clin Oncol 2000;18:94–101.
Olivotto IA, Chua B, Elliott EA, et al. A clinical trial of breast radiation therapy versus breast plus regional radiation therapy in early-stage breast cancer: the MA20 trial. Clin Breast Cancer 2003;4:361–363.
Fastner G, Sedlmayer F, Widder J, et al. Endocrine therapy with or without whole breast irradiation in low-risk breast cancer patients after breast-conserving surgery: 10-year results of the Austrian Breast and Colorectal Cancer Study Group 8A trial. Eur J Cancer 2020;127:12–20.
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 early breast cancer. N Engl J Med 2023;388:585–594.
Whelan TJ, Smith S, Parpia S, et al. Omitting radiotherapy after breast-conserving surgery in luminal A breast cancer. N Engl J Med 2023;389:612–619.
Evidence-Based Reviews in Surgery. Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer. Available at: https://ebrs.online/courses/omitting-radiotherapy-after-breast-conserving-surgery-breast-cancer/ . Accessed January 26, 2024.
Kunkler IH, Williams LJ, Jack WJ, 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.
Jagsi R, Griffith KA, Harris EE, et al. Omission of radiotherapy after breast-conserving surgery for women with breast cancer with low clinical and genomic risk: 5-year outcomes of IDEA. J Clin Oncol 2023;42:390–398.
Braunstein LZ, Wong J, Dillon DA, et al. Abstract OTI-12-02: preliminary report of 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 . Cancer Res 2023;83:OT1-12-02.
Breastcancertrials.org.au. ANZ 1601/BIG 16-02: EXPERT aims to improve personalised use of radiation therapy in early breast cancer patients by using a genomic test to identify women who can safely avoid this treatment after surgery and the possible side effects. Boon Chua, study chair. Available at: https://www.breastcancertrials.org.au/trials/expert/ . Accessed January 24, 2024.
Cancer Research UK. Charlotte Coles, study PI. A study looking at radiotherapy for women with a very small risk of their breast cancer returning (PRIMETIME). Available at: https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/study-radiotherapy-women-small-risk-breast-cancer-returning-primetime . Accessed January 24, 2024.
Nielsen TO, Leung SCY, Rimm DL, et al. Assessment of Ki67 in breast cancer: updated recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst 2021;113:808–819.
Focke CM, Bürger H, van Diest PJ, et al. Interlaboratory variability of Ki67 staining in breast cancer. Eur J Cancer 2017;84:219–227.
Martelli G, Barretta F, Miceli R, et al. Sentinel node biopsy alone or with axillary dissection in breast cancer patients after primary chemotherapy: long-term results of a prospective interventional study. Ann Surg 2022;276:e544–e552.
International Breast Cancer Study Group. Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group trial 10-93. J Clin Oncol 2006;24:337–344.
Choosing Wisely, Society of Surgical Oncology. Five Things Physicians and Patients Should Question. Available at: SSO-5things-List_2020-Updates-11-2020.pdf . Accessed January 24, 2024.
The American Society of Breast Surgeons. Consensus statement on axillary management for patients with in-situ and invasive breast cancer: a concise overview. Available at: https://www.breastsurgeons.org/docs/statements/management-of-the-axilla.pdf . Accessed January 24, 2024.
Brackstone M, Baldassarre FG, Perera FE, et al. Management of the axilla in early-stage breast cancer: Ontario Health (Cancer Care Ontario) and ASCO guideline. J Clin Oncol 2021;39:3056–3082.
Gentilini OD, Botteri E, Sangalli C, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes the SOUND randomized clinical trial. JAMA Oncol 2023;9:1557–1564.
Reimer T, Stachs A, Veselinovic K, et al. Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): a randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer. EClinicalMedicine 2023;55:101756.
Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys 2014;88:553–564.
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015;386:1341–1352.
University of Cambridge. NHS Predict Breast Cancer. Available at: https://breast.predict.nhs.uk/tool . Accessed January 24, 2024.
Buszek SM, Lin HY, Bedrosian I, et al. Lumpectomy plus hormone or radiation therapy alone for women aged 70 years or older with hormone receptor-positive early stage breast cancer in the modern era: an analysis of the National Cancer Database. Int J Radiat Oncol Biol Phys 2019;105:795–802.
Joseph K, Zebak S, Alba V, et al. Adjuvant breast radiotherapy, endocrine therapy, or both after breast conserving surgery in older women with low-risk breast cancer: results from a population-based study. Radiother Oncol 2021;154:93–100.
Dahn H, Wilke D, Walsh G, Pignol J-P. Radiation and/or endocrine therapy? Recurrence and survival outcomes in women over 70 with early breast cancer after breast-conserving surgery. Breast Cancer Res Treat 2020;182:411–420.
Williams LJ, Kunkler IH, King CC, et al. A randomised controlled trial of post-operative radiotherapy following breast-conserving surgery in a minimum-risk population. Quality of life at 5 years in the PRIME trial. Health Technol Assess 2011;15: i–xi, 1.
Murray Brunt A, Haviland JS, Wheatley DA, 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;395:1613–1626.
Ferreira AR, Di Meglio A, Pistilli B, et al. Differential impact of endocrine therapy and chemotherapy on quality of life of breast cancer survivors: a prospective patient-reported outcomes analysis. Ann Oncol 2019;30:1784–1795.
Meattini I, Poortmans PMP, Marrazzo L, et al. Exclusive endocrine therapy or partial breast irradiation for women aged ≥70 years with luminal A-like early stage breast cancer (NCT04134598 EUROPA): proof of concept of a randomized controlled trial comparing health related quality of life by patient reported outcome measures. J Geriatr Oncol 2021;12:182–189.
Owusu C, Buist DS, Field TS, et al. Predictors of tamoxifen discontinuation among older women with estrogen receptor-positive breast cancer. J Clin Oncol 2008;26:549–555.
Hershman DL, Kushi LH, Shao T, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 2010;28:4120–4128.
Nabieva N, Kellner S, Fehm T, et al. Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients. Ann Oncol 2018;29:186–192.
Matar R, Sevilimedu V, Gemignani ML, Morrow M. Impact of endocrine therapy adherence on outcomes in elderly women with early-stage breast cancer undergoing lumpectomy without radiotherapy. Ann Surg Oncol 2022;29:4753–4760.
Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 2017;377:1836–1846.
