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Older age and comorbidity in breast cancer: is RT alone the new therapeutic frontier?

  • Original Article – Cancer Research
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Abstract

Aim

To assess the impact of age, comorbidities and endocrine therapy (ET) in older breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT).

Methods

From June 2009 to December 2017, we enrolled in this study 735 ER-positive BC patients (stage pT1–T2, pNx–1, M0 and age ≥ 65 years) receiving hypo-RT and followed them until September 2019. Baseline comorbidities included in the hypertension-augmented Charlson Comorbidity Index were retrospectively retrieved. Logistic regression model estimated adjusted-odds ratios (ORs) of ET prescription in relation to baseline patient and tumor characteristics. Competing risk analysis estimated 5-year cumulative incidence function (CIF) of ET discontinuation due to side effects (with BC progression or death as competing events), and its effect on locoregional recurrence (LRR) and distant metastasis (DM) (with death as competing event).

Results

ET has been prescribed in 89% patients. In multivariable analysis, the odds of ET prescription was significantly reduced in older patients (≥ 80 years, OR 0.08, 95% CI 0.03–0.20) and significantly increased in patients with moderate comorbidity. Patients ≥ 80 years discontinued the prescribed therapy earlier and more frequently than younger (65–69 years) patients (p = 0.060). Five-year CIF of LLR, DM and death from causes other that BC were 1.7%, 2.2% and 7.5%, respectively. Patients who discontinued ET had higher chance of LRR (p = 0.004). ET use did not impact on OS in any of the analyzed groups.

Conclusions

In older patients, ET did not show a benefit in terms of overall survival. Further studies focusing on tailored treatment approaches are warranted to offer the best care in terms of adjuvant treatment to these patients.

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References

  • A prospective cohort study evaluating risk of local recurrence following breast conserving surgery and endocrine therapy in low risk LUMINAL A Breast cancer (LUMINA) at ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT01791829.

  • Austin PC, Lee DS, Fine JP (2016) Introduction to the analysis of survival data in the presence of competing risks. Circulation 133(6):601–609. https://doi.org/10.1161/CIRCULATIONAHA.115.017719

    Article  PubMed  PubMed Central  Google Scholar 

  • Bartelink H, Maingon P, Poortmans P, Weltens C, Fourquet A, Jager J et al (2015) Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol 16:47–56. https://doi.org/10.1016/S1470-2045(14)71156-8

    Article  PubMed  Google Scholar 

  • Blamey RW, Bates T, Chetty U et al (2013a) Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial. Eur J Cancer 49:2294–2302

    Article  CAS  PubMed  Google Scholar 

  • Blamey RW, Ellis IO, Pinder SE et al (2013b) Survival of invasive breast cancer according to the Notthingham Prognostic Index in cases diagnosed in 1990–1999. Eur J Cancer 43:1548–1555

    Article  Google Scholar 

  • Braithwaite D, Tammemagi CM, Moore DH, Ozanne EM, Hiatt RA, Belkora J et al (2009) Hypertension is an independent predictor of survival disparity between African-American and white breast cancer patients. Int J Cancer 124(5):1213–1219. https://doi.org/10.1002/ijc.24054

    Article  CAS  PubMed  Google Scholar 

  • Cao KI, Salviat F, Laki F, Falcou MC, Carton M, Poortmans P et al (2018) Outcomes of postoperative radiation therapy for breast cancer in older women according to age and comorbidity status: an observational retrospective study in 752 patients. J Geriatric Oncol 9(6):600–605. https://doi.org/10.1016/j.jgo.2018.02.008

    Article  Google Scholar 

  • Carlson RW, McCormick B (2005) Update: NCCN breast cancer clinical practice guidelines. J Natl Comp Cancer Network 3(Suppl. 1):S7–S11

    Google Scholar 

  • Curigliano G, Burstein HJ, P Winer E, Gnant M, Dubsky P, Loibl S et al (2017) De-escalating and escalating treatments for early-stage breast cancer: the St Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol 28(8):1700–1712. doi: 10.1093/annonc/mdx308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Santis MC, Bonfantini F, Di Salvo F, Fiorentino A, Dispinzieri M, Caputo M et al (2018) Hypofractionated whole-breast irradiation with or without boost in elderly patients: clinical evaluation of an Italian experience. Clin Breast Cancer 18(5):e1059–e1066. https://doi.org/10.1016/j.clbc.2018.04.003

    Article  PubMed  Google Scholar 

  • DeGlas NA, Kiderlen M, Vandenbroucke JP, de Craen AJ, Portielje JE, van de Velde CJ, Liefers GJ, Bastiaannet E, Le Cessie S (2015) Performing survival analyses in the presence of competing risks: a clinical example in older breast cancer patients. J Natl Cancer Inst 108(5):366

    Article  Google Scholar 

  • Dispinzieri M, La Rocca E, Meneghini E, Fiorentino A, Lozza L, Di Cosimo S et al (2018) Discontinuation of hormone therapy for elderly breast cancer patients after hypofractionated whole-breast radiotherapy. Med Oncol 35(7):107. https://doi.org/10.1007/s12032-018-1165-9

    Article  PubMed  Google Scholar 

  • Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Darby S, Mc Gale 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 on individual patient data for 10,801 women in 17 randomized trials. Lancet Oncol. 378:1707–1716. doi: 10.1016/S0140-6736(11)61629-2

  • Eaton BR, Jiang R, Torres MA, Kahn ST, Godette K, Lash TL et al (2016) Benefit of adjuvant radiotherapy after breast-conserving therapy among elderly women with T1–T2N0 estrogen receptor-negative breast cancer. Cancer 122(19):3059–3068. https://doi.org/10.1002/cncr.30142

    Article  CAS  PubMed  Google Scholar 

  • Feuer EJ, Wun LM, Boring CC, Flanders WD, Timmel MJ, Tong T (1993) The lifetime risk of developing breast cancer. J Natl Cancer Inst 85:892–897

    Article  CAS  PubMed  Google Scholar 

  • Fiorentino A, Mazzola R, GiajLevra N, Fersino S, Ricchetti F, Di Paola G et al (2018) Comorbidities and intensity-modulated radiotherapy with simultaneous integrated boost in elderly breast cancer patients. Aging Clin Exp Res 30(5):533–538. https://doi.org/10.1007/s40520-017-0802-z

    Article  PubMed  Google Scholar 

  • Meattini I et al (2020) Exclusive endocrine Therapy or Partial Breast Irradiation for women age ≥ 70 years with Luminal-A early breast cancer EUROPA at ClinicalTrials.gov. https://clinicaltrial.gov/ct2/show/NCT04134598

  • Franco P, Iorio GC, Bartoncini S et al (2018) De-escalation of breast radiotherapy after conserving surgery in low-risk early breast cancer patients. Med Oncol 35:62

    Article  PubMed  Google Scholar 

  • Franco P, De Rose F, De Santis MC, Pasinetti N, Lancellotta V, Meduri B, Meattini I; Clinical Oncology Breast Cancer Group (COBCG) Investigators (2020) Omission of postoperative radiation after breast conserving surgery: a progressive paradigm shift towards precision medicine. Clin Transl Radiat Oncol 21:112–119. https://doi.org/10.1016/j.ctro.2020.02.003(eCollection 2020 Mar. Review)

    Article  Google Scholar 

  • Fyles AW, McCready DR, Lee A et al (2004) Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med 351(10):963–970

    Article  CAS  PubMed  Google Scholar 

  • Giordano SH (2012) Radiotherapy in older women with low-risk breast cancer: why did practice not change? J Clin Oncol 30(14):1577–1578

    Article  PubMed  Google Scholar 

  • Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ et al (2013) The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol 14:1086–1094. https://doi.org/10.1016/S1470-2045(13)70386-3

    Article  PubMed  Google Scholar 

  • Herskovic AC, Wu X, Christos PJ, Nagar H (2018) Omission of adjuvant radiotherapy in the elderly breast cancer patient: missed opportunity? Clin Breast Cancer 18(5):418–431. https://doi.org/10.1016/j.clbc.2018.02.006

    Article  PubMed  Google Scholar 

  • Hughes KS, Schnaper LA, Berry D et al (2004) Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351(10):971–977

    Article  CAS  PubMed  Google Scholar 

  • Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA (2013) 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 31(19):2382–2387. https://doi.org/10.1200/JCO.2012.45.2615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirwan CC, Coles CE, Bliss J (2016) It’s PRIMETIME. Postoperative avoidance of radiotherapy: biomarker selection of women at very low risk of local recurrence. Clin Oncol 28:594–596

    Article  CAS  Google Scholar 

  • Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM et al (2015) 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 16(3):266–273. https://doi.org/10.1016/S1470-2045(14)71221-5

    Article  PubMed  Google Scholar 

  • La Rocca E, Meneghini E, Dispinzieri M, Fiorentino A, Bonfantini F, Di Cosimo S, Gennaro M, Cosentino V, Sant M, Pignoli E, Valdagni R, Lozza L, De Santis MC (2019) Hypofractionated irradiation in 794 elderly breast cancer patients: An observational study. Breast J. https://doi.org/10.1111/tbj.13489

    Article  PubMed  Google Scholar 

  • Lievens Y (2010) Hypofractionated breast radiotherapy: financial and economic consequences. Breast 19:192–197

    Article  PubMed  Google Scholar 

  • Monten C, Lievens Y (2018) Adjuvant breast radiotherapy: how to trade- off cost and effectiveness? RadiotherOncol 126:132–138

    Google Scholar 

  • Offersen BV, Boersma LJ, KirkoveC HS, Aznar MC, Sola AB et al (2015) ESTRO consensus guideline on target volume delineation for elective radiation therapy of early-stage breast cancer. Radiother Oncol 114(1):3–10. https://doi.org/10.1016/j.radonc.2014.11.030

    Article  PubMed  Google Scholar 

  • Partridge AH, Wang PS, Winer EP et al (2003) Non adherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol 21:602–606

    Article  CAS  PubMed  Google Scholar 

  • Potter R, Gnant M, Kwasny W et al (2007) Lumpectomy plus tamoxifen or anastrozole with or without whole breast irradiation in women with favorable early breast cancer. Int J Radiat Oncol Biol Phys 68:334–340

    Article  PubMed  Google Scholar 

  • Saleh RR, Nadler MB, Desnoyers A, Rodin DL, Abdel-Qadir H, Amir E (2020) Influence of competing risks on estimates of recurrence risk and breast cancer-specific mortality in analyses of the early breast cancer trialists collaborative group. Sci Rep 10(1):4091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumors, 7th edn. Wiley-Blackwell, Oxford, p 310

    Google Scholar 

  • The IDEA (Individualized Decisions for Endocrine therApy) study at ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02400190

  • The PRECISION (profiling early breast cancer for radiotherapy omission) trial at ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02653755

  • TROG 16.04, ANZ 1601/BIG16–02 EXPERT trial. Examining personilised radiation therapy for low-risk early breast cancer at TROG.com; https://www.trog.com.au/1604-EXPERT

  • Tinterri C, Gatzemeier W, Costa A, Gentilini MA, Zanini V, Regolo L et al (2014) Breast-conservative surgery with and without radiotherapy in patients aged 55–75 years with early-stage breast cancer: a prospective, randomized, multicenter trial analysis after 108 months of median follow-up. Ann Surg Oncol 21(2):408–415. https://doi.org/10.1245/s10434-013-3233-x

    Article  CAS  PubMed  Google Scholar 

  • Ward MC, Vicini F, Chadha M, Pierce L, Recht A, Hayman J, Thaker NG, Khan A, Keisch M (2019a) Shah C (2019) Radiation therapy without hormone therapy for women age 70 or above with low-risk early breast cancer: a microsimulation. Int J Radiat Oncol Biol Phys 105(2):296–306. https://doi.org/10.1016/j.ijrobp.2019.06.014

    Article  PubMed  Google Scholar 

  • Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S et al (2010) Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 362:513–520. https://doi.org/10.1056/NEJMoa0906260

    Article  CAS  PubMed  Google Scholar 

  • Winzer KJ, Sauer R (2004) Sauerbrei Radiation therapy after breast-conserving surgery: first results of a randomised clinical trial in patients with low risk of recurrence. Eur J Cancer 40:998–1005

    Article  PubMed  Google Scholar 

  • Winzer K-J, Sauerbrei W, Braun M et al (2010) Radiation therapy and tamoxifen after breast-conserving surgery: updated results of a 22 randomised clinical trial in patients with low risk of recurrence. Eur J Cancer 46:95–101

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Valenti Cristiana for revision of the English Language.

Author information

Authors and Affiliations

  1. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    E. La Rocca, A. Vitullo, C. Giandini & R. Valdagni

  2. Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

    E. La Rocca, L. Lozza, A. Vitullo, C. Giandini & Maria Carmen De Santis

  3. Analytical Epidemiology and Health Impact Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

    E. Meneghini & M. Sant

  4. Department of Radiation Oncology, Regional General Hospital “F Miulli”, Acquaviva delle Fonti, BA, Italy

    A. Fiorentino

  5. Medical Physics Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

    F. Bonfantini & E. Pignoli

  6. Department of Applied Research and Technological Development DRAST, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

    S. Di Cosimo

  7. Breast Surgery Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

    M. Gennaro

  8. Radiation Oncology 1 and Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

    R. Valdagni

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  1. E. La Rocca
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  2. E. Meneghini
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  10. M. Sant
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  13. Maria Carmen De Santis
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Corresponding author

Correspondence to Maria Carmen De Santis.

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We declare that we do not have any conflict of interest.

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Ethical approval the present study has been reviewed and approved by the Internal Review Board of the Department of Radiation Oncology 1 of National Cancer Institute, Milan, Italy.

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Research involving in human and animal rights. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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La Rocca, E., Meneghini, E., Lozza, L. et al. Older age and comorbidity in breast cancer: is RT alone the new therapeutic frontier?. J Cancer Res Clin Oncol 146, 1791–1800 (2020). https://doi.org/10.1007/s00432-020-03243-5

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  • DOI: https://doi.org/10.1007/s00432-020-03243-5

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