Advertisement

Breast cancer treatment and its effects on aging

  • Leslie Chang
    Affiliations
    Departments of Family Medicine & Public Health, School of Medicine, University of California, San Diego, United States

    Department of Internal Medicine, School of Medicine University of California, San Diego, United States
    Search for articles by this author
  • Lauren S. Weiner
    Affiliations
    Departments of Family Medicine & Public Health, School of Medicine, University of California, San Diego, United States

    University of California San Diego, Moores Cancer Center, La Jolla, CA, United States
    Search for articles by this author
  • Sheri J. Hartman
    Affiliations
    Departments of Family Medicine & Public Health, School of Medicine, University of California, San Diego, United States

    University of California San Diego, Moores Cancer Center, La Jolla, CA, United States
    Search for articles by this author
  • Steve Horvath
    Affiliations
    Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, United States

    Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, United States
    Search for articles by this author
  • Dilip Jeste
    Affiliations
    Departments of Psychiatry & Neuroscience, University of California, San Diego, United States

    Sam and Rose Stein Institute for Research on Aging, United States
    Search for articles by this author
  • Paul S. Mischel
    Affiliations
    Department of Pathology, School of Medicine, University of California, San Diego, United States

    Ludwig Institute for Cancer Research, University of California, San Diego, United States
    Search for articles by this author
  • Deborah M. Kado
    Correspondence
    Corresponding author at: Department of Family Medicine, Public Health and Internal Medicine, University of California, San Diego, United States.
    Affiliations
    Departments of Family Medicine & Public Health, School of Medicine, University of California, San Diego, United States

    Department of Internal Medicine, School of Medicine University of California, San Diego, United States

    Sam and Rose Stein Institute for Research on Aging, United States
    Search for articles by this author
Published:August 02, 2018DOI:https://doi.org/10.1016/j.jgo.2018.07.010

      Abstract

      Breast cancer is the most common cancer of women in the United States. It is also proving to be one of the most treatable. Early detection, surgical intervention, therapeutic radiation, cytotoxic chemotherapies and molecularly targeted agents are transforming the lives of patients with breast cancer, markedly improving their survival. Although current breast cancer treatments are largely successful in producing cancer remission and extending lifespan, there is concern that these treatments may have long lasting detrimental effects on cancer survivors, in part, through their impact on non-tumor cells. Presently, the impact of breast cancer treatment on normal cells, its impact on cellular function and its effect on the overall function of the individual are incompletely understood. In particular, it is unclear whether breast cancer and/or its treatments are associated with an accelerated aging phenotype. In this review, we consider breast cancer survivorship from the perspective of accelerated aging, and discuss the evidence suggesting that women treated for breast cancer may suffer from an increased rate of physical and cognitive decline that likely corresponds with underlying vulnerabilities of genome instability, epigenetic changes, and cellular senescence.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Geriatric Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2017.
        CA Cancer J Clin. 2017; 67 (Epub 2017/01/06) (PubMed PMID: 28055103): 7-30
        • López-Otín C.
        • Blasco M.A.
        • Partridge L.
        • Serrano M.
        • Kroemer G.
        The hallmarks of aging.
        Cell. 2013; 153 (PubMed PMID: 23746838; PMCID: PMC3836174): 1194-1217https://doi.org/10.1016/j.cell.2013.05.039
        • Hanahan D.
        • Weinberg R.A.
        Hallmarks of cancer: the next generation.
        Cell. 2011; 144 (PubMed PMID: 21376230): 646-674https://doi.org/10.1016/j.cell.2011.02.013
        • Reimer T.
        • Gerber B.
        Quality-of-life considerations in the treatment of early-stage breast cancer in the elderly.
        Drugs Aging. 2010; 27 (PubMed PMID: 20883059): 791-800https://doi.org/10.2165/11584700-000000000-00000
        • Cohen H.J.
        • Lan L.
        • Archer L.
        • Kornblith A.B.
        Impact of age, comorbidity and symptoms on physical function in long-term breast cancer survivors (CALGB 70803).
        J Geriatr Oncol. 2012; 3 (82-9). (PubMed PMID: 22707996; PMCID: PMC3375059)https://doi.org/10.1016/j.jgo.2012.01.005
        • Smith A.W.
        • Alfano C.M.
        • Reeve B.B.
        • Irwin M.L.
        • Bernstein L.
        • Baumgartner K.
        • Bowen D.
        • McTiernan A.
        • Ballard-Barbash R.
        Race/ethnicity, physical activity, and quality of life in breast cancer survivors.
        Cancer Epidemiol Biomarkers Prev. 2009; 18 (PubMed PMID: 19190157; PMCID: PMC3031117): 656-663https://doi.org/10.1158/1055-9965.EPI-08-0352
        • Wampler M.A.
        • Topp K.S.
        • Miaskowski C.
        • Byl N.N.
        • Rugo H.S.
        • Hamel K.
        Quantitative and clinical description of postural instability in women with breast cancer treated with taxane chemotherapy.
        Arch Phys Med Rehabil. 2007; 88 (PubMed PMID: 17678662): 1002-1008https://doi.org/10.1016/j.apmr.2007.05.007
        • Von Ah D.
        • Russell K.M.
        • Storniolo A.M.
        • Carpenter J.S.
        Cognitive dysfunction and its relationship to quality of life in breast cancer survivors.
        Oncol Nurs Forum. 2009; 36 (PubMed PMID: 44460586): 326-334
        • Paraskevi T.
        Quality of life outcomes in patients with breast cancer.
        Oncol Rev. 2012; 6 (PubMed PMID: 25992204; PMCID: PMC4419638)https://doi.org/10.4081/oncol.2012.e2
        • Rowland J.H.
        • Bellizzi K.M.
        Cancer survivorship issues: life after treatment and implications for an aging population.
        J Clin Oncol. 2014; 32 (PubMed PMID: 25071099): 2662-2668https://doi.org/10.1200/jco.2014.55.8361
        • Ciambrone D.
        Treatment decision-making among older women with breast cancer.
        J Women Aging. 2006; 18: 31-47https://doi.org/10.1300/J074v18n04_04
        • Puts M.T.E.
        • Tapscott B.
        • Fitch M.
        • Howell D.
        • Monette J.
        • Wan-Chow-Wah D.
        • Krzyzanowska M.
        • Leighl N.B.
        • Springall E.
        • Alibhai S.M.
        A systematic review of factors influencing older adults' decision to accept or decline cancer treatment.
        Cancer Treat Rev. 2015; 41: 197-215https://doi.org/10.1016/j.ctrv.2014.12.010
        • Turner K.M.
        • Deshpande V.
        • Beyter D.
        • Koga T.
        • Rusert J.
        • Lee C.
        • Li B.
        • Arden K.
        • Ren B.
        • Nathanson D.A.
        • Kornblum H.I.
        • Taylor M.D.
        • Kaushal S.
        • Cavenee W.K.
        • Wechsler-Reya R.
        • Furnari F.B.
        • Vandenberg S.R.
        • Rao P.N.
        • Wahl G.M.
        • Bafna V.
        • Mischel P.S.
        Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity.
        Nature. 2017; 543 (Epub 2017/02/09) (PubMed PMID: 28178237; PMCID: PMC5334176): 122-125
        • Tidwell T.R.
        • Soreide K.
        • Hagland H.R.
        Aging, Metabolism, and Cancer Development: from Peto's Paradox to the Warburg Effect.
        Aging Dis. 2017; 8 (Epub 2017/10/03) (PubMed PMID: 28966808; PMCID: PMC5614328): 662-676
        • de Magalhaes J.P.
        How ageing processes influence cancer.
        Nat Rev Cancer. 2013; 13 (Epub 2013/04/25) (PubMed PMID: 23612461): 357-365
        • Torino F.
        • Barnabei A.
        • De Vecchis L.
        • Sini V.
        • Schittulli F.
        • Marchetti P.
        • Corsello S.M.
        Chemotherapy-induced ovarian toxicity in patients affected by endocrine-responsive early breast cancer.
        Crit Rev Oncol Hematol. 2014; 89 (PubMed PMID: 23953684): 27-42https://doi.org/10.1016/j.critrevonc.2013.07.007
        • Shadyab A.H.
        • Macera C.A.
        • Shaffer R.A.
        • Jain S.
        • Gallo L.C.
        • Gass M.L.
        • Waring M.E.
        • Stefanick M.L.
        • Lacroix A.Z.
        Ages at menarche and menopause and reproductive lifespan as predictors of exceptional longevity in women: the Women's Health Initiative.
        Menopause. 2017; 24 (PubMed PMID: 27465713; PMCID: PMC5177476): 35-44https://doi.org/10.1097/GME.0000000000000710
        • Peel A.B.
        • Thomas S.M.
        • Dittus K.
        • Jones L.W.
        • Lakoski S.G.
        Cardiorespiratory fitness in breast cancer patients: a call for normative values.
        J Am Heart Assoc. 2014; 3 (PubMed PMID: 24419734; PMCID: PMC3959685): e000432https://doi.org/10.1161/JAHA.113.000432
        • Zambetti M.
        • Moliterni A.
        • Materazzo C.
        • Stefanelli M.
        • Cipriani S.
        • Valagussa P.
        • Bonadonna G.
        • Gianni L.
        Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation.
        J Clin Oncol. 2001; 19 (PubMed PMID: 11134193): 37-43
        • Ganz P.A.
        • Hussey M.A.
        • Moinpour C.M.
        • Unger J.M.
        • Hutchins L.F.
        • Dakhil S.R.
        • Giguere J.K.
        • Goodwin J.W.
        • Martino S.
        • Albain K.S.
        Late cardiac effects of adjuvant chemotherapy in breast cancer survivors treated on Southwest Oncology Group protocol s8897.
        J Clin Oncol. 2008; 26 (PubMed PMID: 18227530): 1223-1230https://doi.org/10.1200/JCO.2007.11.8877
        • Doyle J.J.
        • Neugut A.I.
        • Jacobson J.S.
        • Grann V.R.
        • Hershman D.L.
        Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study.
        J Clin Oncol. 2005; 23 (PubMed PMID: 16314622): 8597-8605https://doi.org/10.1200/JCO.2005.02.5841
        • Gianni L.
        • Herman E.H.
        • Lipshultz S.E.
        • Minotti G.
        • Sarvazyan N.
        • Sawyer D.B.
        Anthracycline cardiotoxicity: from bench to bedside.
        J Clin Oncol. 2008; 26 (PubMed PMID: 18669466; PMCID: PMC3018290): 3777-3784https://doi.org/10.1200/JCO.2007.14.9401
        • Pinder M.C.
        • Duan Z.
        • Goodwin J.S.
        • Hortobagyi G.N.
        • Giordano S.H.
        Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer.
        J Clin Oncol. 2007; 25 (PubMed PMID: 17664460): 3808-3815https://doi.org/10.1200/JCO.2006.10.4976
        • Bouvard B.
        • Soulié P.
        • Hoppé E.
        • Georgin-Mege M.
        • Royer M.
        • Mesgouez-Nebout N.
        • Lassalle C.
        • Cellier P.
        • Jadaud E.
        • Abadie-Lacourtoisie S.
        • Tuchais C.
        • Vinchon-Petit S.
        • Audran M.
        • Chappard D.
        • Legrand E.
        Fracture incidence after 3 years of aromatase inhibitor therapy.
        Ann Oncol. 2014; 25 (PubMed PMID: 24608193): 843-847https://doi.org/10.1093/annonc/mdu008
        • Vanderwalde A.
        • Hurria A.
        Aging and osteoporosis in breast and prostate cancer.
        A Cancer J Clin. 2011; 61 (PubMed PMID: 2011055522. Language: English. Entry Date: 20110715. Revision Date: 20120302. Publication Type: journal article. Journal Subset: Biomedical): 139-156https://doi.org/10.3322/caac.20103
        • Brufsky A.M.
        Cancer treatment-induced bone loss: pathophysiology and clinical perspectives.
        Oncologist. 2008; 13 (PubMed PMID: 18305064): 187-195https://doi.org/10.1634/theoncologist.2007-0152
        • Balducci L.
        Bone complications of cancer treatment in the elderly.
        Oncology (Williston Park). 2010; 24 (PubMed PMID: 20718254): 741-747
        • Ward P.R.
        • Wong M.D.
        • Moore R.
        • Naeim A.
        Fall-related injuries in elderly cancer patients treated with neurotoxic chemotherapy: a retrospective cohort study.
        J Geriatr Oncol. 2014; 5 (Epub 2013/11/08) (PubMed PMID: 24484719): 57-64
        • Vardy J.
        Cognitive function in breast cancer survivors.
        Cancer Treat Res. 2009; 151 (PubMed PMID: 19593525): 387-419https://doi.org/10.1007/978-0-387-75115-3_24
        • Janelsins M.C.
        • Kesler S.R.
        • Ahles T.A.
        • Morrow G.R.
        Prevalence, mechanisms, and management of cancer-related cognitive impairment.
        Int Rev Psychiatry. 2014; 26 (PubMed PMID: 24716504; PMCID: PMC4084673): 102-113https://doi.org/10.3109/09540261.2013.864260
        • Wefel J.S.
        • Kesler S.R.
        • Noll K.R.
        • Schagen S.B.
        Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults.
        CA Cancer J Clin. 2015; 65 (PubMed PMID: 25483452; PMCID: PMC4355212): 123-138https://doi.org/10.3322/caac.21258
        • Ahles T.A.
        • Root J.C.
        • Ryan E.L.
        Cancer- and cancer treatment-associated cognitive change: an update on the state of the science.
        J Clin Oncol. 2012; 30 (Epub 2012/09/26) (PubMed PMID: 23008308; PMCID: PMC3675678): 3675-3686
        • Koppelmans V.
        • Breteler M.M.
        • Boogerd W.
        • Seynaeve C.
        • Gundy C.
        • Schagen S.B.
        Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy.
        J Clin Oncol. 2012; 30 (Epub 2012/03/01) (PubMed PMID: 22370315): 1080-1086
        • Wefel J.S.
        • Saleeba A.K.
        • Buzdar A.U.
        • Meyers C.A.
        Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer.
        Cancer. 2010; 116 (Epub 2010/06/22) (PubMed PMID: 20564075): 3348-3356
      1. Conroy SK, McDonald BC, Smith DJ, Moser LR, West JD, Kamendulis LM, Klaunig JE, Champion VL, Unverzagt FW, Saykin AJ. Alterations in brain structure and function in breast cancer survivors: effect of post-chemotherapy interval and relation to oxidative DNA damage. Breast cancer research and treatment. 2013;137(2):493–502. doi: https://doi.org/10.1007/s10549-012-2385-x. (PubMed PMID: 23263697; PMCID: PMC3543695).

        • de Ruiter M.B.
        • Reneman L.
        • Boogerd W.
        • Veltman D.J.
        • van Dam F.S.A.M.
        • Nederveen A.J.
        • Boven E.
        • Schagen S.B.
        Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer.
        Hum Brain Mapp. 2011; 32: 1206-1219https://doi.org/10.1002/hbm.21102
        • Kesler S.R.
        • Kent J.S.
        • O'Hara R.
        Prefrontal cortex and executive function impairments in primary breast cancer.
        Arch Neurol. 2011; 68https://doi.org/10.1001/archneurol.2011.245
        • Kesler S.R.
        • Watson C.L.
        • Blayney D.W.
        Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.
        Neurobiol Aging. 2015; 36 (PubMed PMID: 26004016; PMCID: PMC4464941): 2429-2442https://doi.org/10.1016/j.neurobiolaging.2015.04.015
        • Lange M.
        • Giffard B.
        • Noal S.
        • Rigal O.
        • Kurtz J.-E.
        • Heutte N.
        • Lévy C.
        • Allouache D.
        • Rieux C.
        • Fel J.L.
        • Daireaux A.
        • Clarisse B.
        • Veyret C.
        • Barthélémy P.
        • Longato N.
        • Eustache F.
        • Joly F.
        Baseline cognitive functions among elderly patients with localised breast cancer.
        Eur J Cancer. 2014; 50: 2181-2189https://doi.org/10.1016/j.ejca.2014.05.026
        • Mandelblatt J.S.
        • Stern R.A.
        • Luta G.
        • McGuckin M.
        • Clapp J.D.
        • Hurria A.
        • Jacobsen P.B.
        • Faul L.A.
        • Isaacs C.
        • Denduluri N.
        • Gavett B.
        • Traina T.A.
        • Johnson P.
        • Silliman R.A.
        • Turner R.S.
        • Howard D.
        • Meter J.W.V.
        • Saykin A.
        • Ahles T.
        Cognitive impairment in older patients with breast cancer before systemic therapy: is there an interaction between cancer and comorbidity?.
        J Clin Oncol. 2014; 32 (PubMed PMID: 24841981): 1909-1918https://doi.org/10.1200/jco.2013.54.2050
        • Von Ah D.
        Cognitive function in breast cancer survivors compared to healthy age- and education-matched women.
        . 2009; 23 (PubMed PMID: 19156566; PMCID: PMC3557514): 661-674https://doi.org/10.1080/13854040802541439
        • Ahles T.A.
        • Saykin A.J.
        • McDonald B.C.
        • Li Y.
        • Furstenberg C.T.
        • Hanscom B.S.
        • Mulrooney T.J.
        • Schwartz G.N.
        • Kaufman P.A.
        Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve.
        J Clin Oncol. 2010; 28 (Epub 2010/09/15) (PubMed PMID: 20837957; PMCID: PMC2988635): 4434-4440
        • Collins B.
        • MacKenzie J.
        • Tasca G.A.
        • Scherling C.
        • Smith A.
        Persistent cognitive changes in breast cancer patients 1 year following completion of chemotherapy.
        J Int Neuropsychol Soc. 2013; 20 (Epub 11/15): 370-379
        • Lepage C.
        • Smith A.M.
        • Moreau J.
        • Barlow-Krelina E.
        • Wallis N.
        • Collins B.
        • MacKenzie J.
        • Scherling C.
        A prospective study of grey matter and cognitive function alterations in chemotherapy-treated breast cancer patients.
        SpringerPlus. 2014; 3: 444https://doi.org/10.1186/2193-1801-3-444
        • Mandelblatt J.S.
        • Clapp J.D.
        • Luta G.
        • Faul L.A.
        • Tallarico M.D.
        • McClendon T.D.
        • Whitley J.A.
        • Cai L.
        • Ahles T.A.
        • Stern R.A.
        • Jacobsen P.B.
        • Small B.J.
        • Pitcher B.N.
        • Dura-Fernandis E.
        • Muss H.B.
        • Hurria A.
        • Cohen H.J.
        • Isaacs C.
        Long-term trajectories of self-reported cognitive function in a cohort of older survivors of breast cancer: CALGB 369901 (Alliance).
        Cancer. 2016; 122: 3555-3563https://doi.org/10.1002/cncr.30208
        • Schagen S.B.
        • Muller M.J.
        • Boogerd W.
        • Mellenbergh G.J.
        • van Dam F.S.
        Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients.
        J Natl Cancer Inst. 2006; 98https://doi.org/10.1093/jnci/djj470
        • Schilder C.M.
        • Seynaeve C.
        • Beex L.V.
        • Boogerd W.
        • Linn S.C.
        • Gundy C.M.
        • Huizenga H.M.
        • Nortier J.W.
        • van de Velde C.J.
        • van Dam F.S.
        • Schagen S.B.
        Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial.
        J Clin Oncol. 2010; 28 (PubMed PMID: 20142601): 1294-1300https://doi.org/10.1200/JCO.2008.21.3553
        • Jim H.S.
        • Phillips K.M.
        • Chait S.
        • Faul L.A.
        • Popa M.A.
        • Lee Y.H.
        • Hussin M.G.
        • Jacobsen P.B.
        • Small B.J.
        Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy.
        J Clin Oncol. 2012; 30 (Epub 2012/08/29) (PubMed PMID: 22927526; PMCID: PMC3462044): 3578-3587
        • Falleti M.G.
        • Sanfilippo A.
        • Maruff P.
        • Weih L.
        • Phillips K.A.
        The nature and severity of cognitive impairment associated with adjuvant chemotherapy in women with breast cancer: a meta-analysis of the current literature.
        Brain Cogn. 2005; 59 (PubMed PMID: 15975700): 60-70
        • Anderson-Hanley C.
        • Sherman M.L.
        • Riggs R.
        • Agocha V.B.
        • Compas B.E.
        Neuropsychological effects of treatments for adults with cancer: a meta-analysis and review of the literature.
        J Int Neuropsychol Soc. 2003; 9 (Epub 2004/01/24) (PubMed PMID: 14738279): 967-982
        • Jansen C.E.
        • Miaskowski C.
        • Dodd M.
        • Dowling G.
        • Kramer J.
        A metaanalysis of studies of the effects of cancer chemotherapy on various domains of cognitive function.
        Cancer. 2005; 104 (Epub 2005/10/06) (PubMed PMID: 16206292): 2222-2233
        • Jansen C.E.
        • Cooper B.A.
        • Dodd M.J.
        • Miaskowski C.A.
        A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients.
        Support Care Cancer. 2011; 19 (Epub 2010/09/08) (PubMed PMID: 20820813): 1647-1656
        • Ono M.
        • Ogilvie J.M.
        • Wilson J.S.
        • Green H.J.
        • Chambers S.K.
        • Ownsworth T.
        • Shum D.H.
        A meta-analysis of cognitive impairment and decline associated with adjuvant chemotherapy in women with breast cancer.
        Front Oncol. 2015; 5 (PubMed PMID: 25806355; PMCID: PMC4354286): 59https://doi.org/10.3389/fonc.2015.00059
        • Jenkins V.
        • Shilling V.
        • Deutsch G.
        • Bloomfield D.
        • Morris R.
        • Allan S.
        • Bishop H.
        • Hodson N.
        • Mitra S.
        • Sadler G.
        • Shah E.
        • Stein R.
        • Whitehead S.
        • Winstanley J.
        A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer.
        Br J Cancer. 2006; 94 (Epub 2006/03/09) (PubMed PMID: 16523200; PMCID: PMC3216421): 828-834
        • Tager F.A.
        • McKinley P.S.
        • Schnabel F.R.
        • El-Tamer M.
        • Cheung Y.K.
        • Fang Y.
        • Golden C.R.
        • Frosch M.E.
        • Habif U.
        • Mulligan M.M.
        • Chen I.S.
        • Hershman D.L.
        The cognitive effects of chemotherapy in post-menopausal breast cancer patients: a controlled longitudinal study.
        Breast Cancer Res Treat. 2010; 123 (PubMed PMID: 19894112): 25-34https://doi.org/10.1007/s10549-009-0606-8
        • Phillips K.A.
        • Ribi K.
        • Fisher R.
        Do aromatase inhibitors have adverse effects on cognitive function?.
        Breast Cancer Res. 2011; 13: 203https://doi.org/10.1186/bcr2806
        • Schilder C.M.T.
        • Seynaeve C.
        • Linn S.C.
        • Boogerd W.
        • Beex L.V.A.M.
        • Gundy C.M.
        • Nortier J.W.R.
        • van de Velde C.J.H.
        • van Dam F.S.A.M.
        • Schagen S.B.
        Self-reported cognitive functioning in postmenopausal breast cancer patients before and during endocrine treatment: findings from the neuropsychological TEAM side-study.
        Psychooncology. 2012; 21: 479-487https://doi.org/10.1002/pon.1928
        • Castellon S.A.
        • Ganz P.A.
        • Bower J.E.
        • Petersen L.
        • Abraham L.
        • Greendale G.A.
        Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen.
        J Clin Exp Neuropsychol. 2004; 26 (Epub 2005/03/04) (PubMed PMID: 15742545): 955-969
        • Merriman J.D.
        • Sereika S.M.
        • Brufsky A.M.
        • McAuliffe P.F.
        • McGuire K.P.
        • Myers J.S.
        • Phillips M.L.
        • Ryan C.M.
        • Gentry A.L.
        • Jones L.D.
        • Bender C.M.
        Trajectories of self-reported cognitive function in postmenopausal women during adjuvant systemic therapy for breast cancer.
        Psychooncology. 2017; 26: 44-52https://doi.org/10.1002/pon.4009
        • Phillips K.A.
        • Aldridge J.
        • Ribi K.
        • Sun Z.
        • Thompson A.
        • Harvey V.
        • Thürlimann B.
        • Cardoso F.
        • Pagani O.
        • Coates A.S.
        • Goldhirsch A.
        • Price K.N.
        • Gelber R.D.
        • Bernhard J.
        Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial.
        Breast Cancer Res Treat. 2011; 126https://doi.org/10.1007/s10549-010-1235-y
        • Collins B.
        • Mackenzie J.
        • Stewart A.
        • Bielajew C.
        • Verma S.
        Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment.
        Psychooncology. 2009; 18 (Epub 2008/06/14) (PubMed PMID: 18551510): 134-143
        • Hermelink K.
        • Untch M.
        • Lux M.P.
        • Kreienberg R.
        • Beck T.
        • Bauerfeind I.
        • Munzel K.
        Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study.
        Cancer. 2007; 109https://doi.org/10.1002/cncr.22610
        • Ahles T.A.
        • Saykin A.J.
        • McDonald B.C.
        • Furstenberg C.T.
        • Cole B.F.
        • Hanscom B.S.
        • Mulrooney T.J.
        • Schwartz G.N.
        • Kaufman P.A.
        Cognitive function in breast cancer patients prior to adjuvant treatment.
        Breast Cancer Res Treat. 2008; 110 (PubMed PMID: 17674194; PMCID: PMC3114441): 143-152https://doi.org/10.1007/s10549-007-9686-5
        • Mather M.
        Aging and cognition.
        Wiley Interdiscip Rev Cogn Sci. 2010; 1 (Epub 2010/05/01) (PubMed PMID: 26271375): 346-362
        • Hebert L.E.
        • Weuve J.
        • Scherr P.A.
        • Evans D.A.
        Alzheimer disease in the United States (2010–2050) estimated using the 2010 census.
        Neurology. 2013; 80 (Epub 2013/02/08) (PubMed PMID: 23390181; PMCID: PMC3719424): 1778-1783
        • Lichtman S.M.
        • Hurria A.
        • Jacobsen P.B.
        Geriatric Oncology: An Overview.
        J Clin Oncol. 2014; 32: 2521-2522https://doi.org/10.1200/jco.2014.57.4822
      2. Surveillance, Epidemiology, and End Results (SEER) Program Populations (1969–2015). 2016
        • Ehlers D.
        • Trinh L.
        • McAuley E.
        The intersection of cancer and aging: implications for physical activity and cardiorespiratory fitness effects on cognition.
        Expert Review of Quality of Life in Cancer Care. 2016; 1: 347-350https://doi.org/10.1080/23809000.2016.1241661
      3. Hurria A, Rosen C, Hudis C, Zuckerman E, Panageas KS, Lachs MS, Witmer M, van Gorp WG, Fornier M, D'Andrea G, Moasser M, Dang C, Van Poznak C, Hurria A, Holland J. Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study. J Am Geriatr Soc 2006;54(6):925–31. Epub 2006/06/17. doi: https://doi.org/10.1111/j.1532-5415.2006.00732.x. PubMed PMID: 16776787.

        • Ahles T.A.
        • Root J.C.
        • Ryan E.L.
        Cancer- and cancer treatment–associated cognitive change: an update on the state of the science.
        J Clin Oncol. 2012; 30 (PubMed PMID: 23008308; PMCID: PMC3675678): 3675-3686https://doi.org/10.1200/jco.2012.43.0116
        • Merriman J.D.
        • Von Ah D.
        • Miaskowski C.
        • Aouizerat B.E.
        Proposed mechanisms for cancer- and treatment-related cognitive. Seminars in oncology nursing.
        . 2013; 29 (PubMed PMID: 24183157; PMCID: PMC3817493)https://doi.org/10.1016/j.soncn.2013.08.006
        • Mandelblatt J.S.
        • Hurria A.
        • McDonald B.C.
        • Saykin A.J.
        • Stern R.A.
        • Vanmeter J.W.
        • McGuckin M.
        • Traina T.
        • Denduluri N.
        • Turner S.
        • Howard D.
        • Jacobsen P.B.
        • Ahles T.
        Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?.
        Semin Oncol. 2013; 40 (Epub 2013/12/18) (PubMed PMID: 24331192; PMCID: PMC3880205): 709-725
        • Debess J.
        • Riis J.O.
        • Engebjerg M.C.
        • Ewertz M.
        Cognitive function after adjuvant treatment for early breast cancer: a population-based longitudinal study.
        Breast Cancer Res Treat. 2010; 121 (Epub 2010/03/23) (PubMed PMID: 20306129): 91-100
        • Janelsins M.C.
        • Heckler C.E.
        • Peppone L.J.
        • Kamen C.
        • Mustian K.M.
        • Mohile S.G.
        • Magnuson A.
        • Kleckner I.R.
        • Guido J.J.
        • Young K.L.
        • Conlin A.K.
        • Weiselberg L.R.
        • Mitchell J.W.
        • Ambrosone C.A.
        • Ahles T.A.
        • Morrow G.R.
        Cognitive complaints in survivors of breast cancer after chemotherapy compared with age-matched controls: an analysis from a nationwide, multicenter, prospective longitudinal study.
        J Clin Oncol. 2017; 35 (PubMed PMID: 28029304): 506-514https://doi.org/10.1200/jco.2016.68.5826
        • Schagen S.B.
        • Muller M.J.
        • Boogerd W.
        • Mellenbergh G.J.
        • van Dam F.S.A.M.
        Change in Cognitive Function After Chemotherapy: a Prospective Longitudinal Study in Breast Cancer Patients.
        JNCI. 2006; 98: 1742-1745https://doi.org/10.1093/jnci/djj470
        • Koppelmans V.
        • de Ruiter M.B.
        • van der Lijn F.
        • Boogerd W.
        • Seynaeve C.
        • van der Lugt A.
        • Vrooman H.
        • Niessen W.J.
        • Breteler M.M.
        • Schagen S.B.
        Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy.
        Breast Cancer Res Treat. 2012; 132 (Epub 2011/12/30) (PubMed PMID: 22205140): 1099-1106
        • de Ruiter M.B.
        • Reneman L.
        • Boogerd W.
        • Veltman D.J.
        • Caan M.
        • Douaud G.
        • Lavini C.
        • Linn S.C.
        • Boven E.
        • van Dam F.S.
        • Schagen S.B.
        Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging.
        Hum Brain Mapp. 2012; 33 (Epub 2011/11/19) (PubMed PMID: 22095746): 2971-2983
        • Deprez S.
        • Amant F.
        • Yigit R.
        • Porke K.
        • Verhoeven J.
        • Van den Stock J.
        • Smeets A.
        • Christiaens M.R.
        • Leemans A.
        • Van Hecke W.
        • Vandenberghe J.
        • Vandenbulcke M.
        • Sunaert S.
        Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients.
        Hum Brain Mapp. 2011; 32 (Epub 2010/08/21) (PubMed PMID: 20725909): 480-493
        • Silverman D.H.S.
        • Dy C.J.
        • Castellon S.A.
        • Lai J.
        • Pio B.S.
        • Abraham L.
        • Waddell K.
        • Petersen L.
        • Phelps M.E.
        • Ganz P.A.
        Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy.
        Breast Cancer Res Treat. 2007; 103: 303-311https://doi.org/10.1007/s10549-006-9380-z
        • Scherling C.
        • Collins B.
        • Mackenzie J.
        • Bielajew C.
        • Smith A.
        Pre-chemotherapy differences in visuospatial working memory in breast cancer patients compared to controls: an FMRI study.
        Front Hum Neurosci. 2011; 5 (Epub 2011/11/05) (PubMed PMID: 22053153; PMCID: PMC3205481): 122
        • Lepage C.
        • Smith A.M.
        • Moreau J.
        • Barlow-Krelina E.
        • Wallis N.
        • Collins B.
        • MacKenzie J.
        • Scherling C.
        A prospective study of grey matter and cognitive function alterations in chemotherapy-treated breast cancer patients.
        Springerplus. 2014; 3 (Epub 2014/09/04) (PubMed PMID: 25184110; PMCID: Pmc4149682): 444
        • Blackburn E.H.
        • Greider C.W.
        • Szostak J.W.
        Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging.
        Nat Med. 2006; 12 (PubMed PMID: 17024208): 1133-1138https://doi.org/10.1038/nm1006-1133
        • Blasco M.A.
        Telomere length, stem cells and aging.
        Nat Chem Biol. 2007; 3 (PubMed PMID: 17876321): 640-649https://doi.org/10.1038/nchembio.2007.38
        • Blackburn E.H.
        • Epel E.S.
        • Lin J.
        Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.
        Science. 2015; 350 (PubMed PMID: 26785477): 1193-1198https://doi.org/10.1126/science.aab3389
        • Ennour-Idrissi K.
        • Maunsell E.
        • Diorio C.
        Telomere length and breast cancer prognosis: a systematic review.
        Cancer Epidemiol Biomarkers Prev. 2017; 26 (Epub 2016/09/27) (PubMed PMID: 27677729): 3-10
        • Hayashi M.T.
        • Cesare A.J.
        • Fitzpatrick J.A.
        • Lazzerini-Denchi E.
        • Karlseder J.
        A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest.
        Nat Struct Mol Biol. 2012; 19 (Epub 2012/03/11) (PubMed PMID: 22407014; PMCID: PMC3319806): 387-394
        • Bratic A.
        • Larsson N.G.
        The role of mitochondria in aging.
        J Clin Invest. 2013; 123 (Epub 2013/03/05) (PubMed PMID: 23454757; PMCID: PMC3582127): 951-957
        • Kraytsberg Y.
        • Kudryavtseva E.
        • McKee A.C.
        • Geula C.
        • Kowall N.W.
        • Khrapko K.
        Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons.
        Nat Genet. 2006; 38 (Epub 2006/04/11) (PubMed PMID): 518-520
        • Ryan M.T.
        • Hoogenraad N.J.
        Mitochondrial-nuclear communications.
        Annu Rev Biochem. 2007; 76 (Epub 2007/01/18) (PubMed PMID: 17227225): 701-722
        • Holzenberger M.
        • Dupont J.
        • Ducos B.
        • Leneuve P.
        • Géloën A.
        • Even P.C.
        • Cervera P.
        • Le Bouc Y.
        IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice.
        Nature. 2003; 421 (PubMed PMID: 12483226): 182-187https://doi.org/10.1038/nature01298
        • Bonawitz N.D.
        • Chatenay-Lapointe M.
        • Pan Y.
        • Shadel G.S.
        Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression.
        Cell Metab. 2007; 5 (Epub 2007/04/04) (PubMed PMID: 17403371; PMCID: PMC3460550): 265-277
        • Pavlides S.
        • Whitaker-Menezes D.
        • Castello-Cros R.
        • Flomenberg N.
        • Witkiewicz A.K.
        • Frank P.G.
        • Casimiro M.C.
        • Wang C.
        • Fortina P.
        • Addya S.
        • Pestell R.G.
        • Martinez-Outschoorn U.E.
        • Sotgia F.
        • Lisanti M.P.
        The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma.
        Cell Cycle. 2009; 8 (Epub 2009/11/20) (PubMed PMID: 19923890): 3984-4001
        • Bonuccelli G.
        • Whitaker-Menezes D.
        • Castello-Cros R.
        • Pavlides S.
        • Pestell R.G.
        • Fatatis A.
        • Witkiewicz A.K.
        • Vander Heiden M.G.
        • Migneco G.
        • Chiavarina B.
        • Frank P.G.
        • Capozza F.
        • Flomenberg N.
        • Martinez-Outschoorn U.E.
        • Sotgia F.
        • Lisanti M.P.
        The reverse Warburg effect: glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts.
        Cell Cycle. 2010; 9 (Epub 2010/05/25) (PubMed PMID: 20495363): 1960-1971
        • Elliott R.L.
        • Jiang X.P.
        • Head J.F.
        Mitochondria organelle transplantation: introduction of normal epithelial mitochondria into human cancer cells inhibits proliferation and increases drug sensitivity.
        Breast Cancer Res Treat. 2012; 136 (Epub 2012/10/20) (PubMed PMID: 23080556): 347-354
        • Ma J.
        • Zhang Q.
        • Chen S.
        • Fang B.
        • Yang Q.
        • Chen C.
        • Miele L.
        • Sarkar F.H.
        • Xia J.
        • Wang Z.
        Mitochondrial dysfunction promotes breast cancer cell migration and invasion through HIF1alpha accumulation via increased production of reactive oxygen species.
        PLoS One. 2013; 8 (Epub 2013/08/08) (PubMed PMID: 23922721; PMCID: PMC3726697): e69485
        • Kaipparettu B.A.
        • Ma Y.
        • Park J.H.
        • Lee T.L.
        • Zhang Y.
        • Yotnda P.
        • Creighton C.J.
        • Chan W.Y.
        • Wong L.J.
        Crosstalk from non-cancerous mitochondria can inhibit tumor properties of metastatic cells by suppressing oncogenic pathways.
        PLoS One. 2013; 8 (Epub 2013/05/15) (PubMed PMID: 23671572; PMCID: PMC3650012): e61747
        • Stolarek R.A.
        • Potargowicz E.
        • Seklewska E.
        • Jakubik J.
        • Lewandowski M.
        • Jeziorski A.
        • Nowak D.
        Increased H2O2 level in exhaled breath condensate in primary breast cancer patients.
        J Cancer Res Clin Oncol. 2010; 136 (PubMed PMID: 19967414): 923-930https://doi.org/10.1007/s00432-009-0734-x
        • Ray G.
        • Batra S.
        • Shukla N.K.
        • Deo S.
        • Raina V.
        • Ashok S.
        • Husain S.A.
        Lipid peroxidation, free radical production and antioxidant status in breast cancer.
        Breast Cancer Res Treat. 2000; 59 (PubMed PMID: 10817351): 163-170
        • Sehl M.E.
        • Henry J.E.
        • Storniolo A.M.
        • Ganz P.A.
        • Horvath S.
        DNA methylation age is elevated in breast tissue of healthy women.
        Breast Cancer Res Treat. 2017; 164 (Epub 2017/03/31) (PubMed PMID: 28364215; PMCID: PMC5487725): 209-219
        • Oberdoerffer P.
        • Sinclair D.A.
        The role of nuclear architecture in genomic instability and ageing.
        Nat Rev Mol Cell Biol. 2007; 8 (PubMed PMID: 17700626): 692-702https://doi.org/10.1038/nrm2238
        • Vandenberk B.
        • Brouwers B.
        • Hatse S.
        • Wildiers H.
        p16INK4a: A central player in cellular senescence and a promising aging biomarker in elderly cancer patients.
        J Geriatr Oncol. 2011; 2: 259-269https://doi.org/10.1016/j.jgo.2011.08.004
        • Liu Y.
        • Sanoff H.K.
        • Cho H.
        • Burd C.E.
        • Torrice C.
        • Ibrahim J.G.
        • Thomas N.E.
        • Sharpless N.E.
        Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging.
        Aging Cell. 2009; 8 (PubMed PMID: 19485966; PMCID: PMC2752333): 439-448https://doi.org/10.1111/j.1474-9726.2009.00489.x
        • Krishnamurthy J.
        • Torrice C.
        • Ramsey M.R.
        • Kovalev G.I.
        • Al-Regaiey K.
        • Su L.
        • Sharpless N.E.
        Ink4a/Arf expression is a biomarker of aging.
        J Clin Invest. 2004; 114 (PubMed PMID: 15520862; PMCID: PMC524230): 1299-1307https://doi.org/10.1172/JCI22475
        • Sanoff H.K.
        • Deal A.M.
        • Krishnamurthy J.
        • Torrice C.
        • Dillon P.
        • Sorrentino J.
        • Ibrahim J.G.
        • Jolly T.A.
        • Williams G.
        • Carey L.A.
        • Drobish A.
        • Gordon B.B.
        • Alston S.
        • Hurria A.
        • Kleinhans K.
        • Rudolph K.L.
        • Sharpless N.E.
        • Muss H.B.
        Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer.
        J Natl Cancer Inst. 2014; 106 (PubMed PMID: 24681605; PMCID: PMC3982894): dju057https://doi.org/10.1093/jnci/dju057
        • Alfano C.M.
        • Peng J.
        • Andridge R.R.
        • Lindgren M.E.
        • Povoski S.P.
        • Lipari A.M.
        • Agnese D.M.
        • Farrar W.B.
        • Yee L.D.
        • Carson W.E.
        • Kiecolt-Glaser J.K.
        Inflammatory cytokines and comorbidity development in breast cancer survivors versus noncancer controls: evidence for accelerated aging?.
        J Clin Oncol. 2017; 35 (Epub 2016/11/28) (PubMed PMID: 27893337; PMCID: PMC5455675): 149-156
        • Perou C.M.
        • Sørlie T.
        • Eisen M.B.
        • van de Rijn M.
        • Jeffrey S.S.
        • Rees C.A.
        • Pollack J.R.
        • Ross D.T.
        • Johnsen H.
        • Akslen L.A.
        • Fluge O.
        • Pergamenschikov A.
        • Williams C.
        • Zhu S.X.
        • Lønning P.E.
        • Børresen-Dale A.L.
        • Brown P.O.
        • Botstein D.
        Molecular portraits of human breast tumours.
        Nature. 2000; 406 (PubMed PMID: 10963602): 747-752https://doi.org/10.1038/35021093
        • van de Vijver M.J.
        • He Y.D.
        • van't Veer L.J.
        • Dai H.
        • Hart A.A.
        • Voskuil D.W.
        • Schreiber G.J.
        • Peterse J.L.
        • Roberts C.
        • Marton M.J.
        • Parrish M.
        • Atsma D.
        • Witteveen A.
        • Glas A.
        • Delahaye L.
        • van der Velde T.
        • Bartelink H.
        • Rodenhuis S.
        • Rutgers E.T.
        • Friend S.H.
        • Bernards R.
        A gene-expression signature as a predictor of survival in breast cancer.
        N Engl J Med. 2002; 347 (PubMed PMID: 12490681): 1999-2009https://doi.org/10.1056/NEJMoa021967
        • van't Veer L.J.
        • Dai H.
        • van de Vijver M.J.
        • He Y.D.
        • Hart A.A.
        • Mao M.
        • Peterse H.L.
        • van der Kooy K.
        • Marton M.J.
        • Witteveen A.T.
        • Schreiber G.J.
        • Kerkhoven R.M.
        • Roberts C.
        • Linsley P.S.
        • Bernards R.
        • Friend S.H.
        Gene expression profiling predicts clinical outcome of breast cancer.
        Nature. 2002; 415 (PubMed PMID: 11823860): 530-536https://doi.org/10.1038/415530a
        • Paik S.
        • Shak S.
        • Tang G.
        • Kim C.
        • Baker J.
        • Cronin M.
        • Baehner F.L.
        • Walker M.G.
        • Watson D.
        • Park T.
        • Hiller W.
        • Fisher E.R.
        • Wickerham D.L.
        • Bryant J.
        • Wolmark N.
        A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
        N Engl J Med. 2004; 351 (PubMed PMID: 15591335): 2817-2826https://doi.org/10.1056/NEJMoa041588
        • Konecny G.
        • Pauletti G.
        • Pegram M.
        • Untch M.
        • Dandekar S.
        • Aguilar Z.
        • Wilson C.
        • Rong H.M.
        • Bauerfeind I.
        • Felber M.
        • Wang H.J.
        • Beryt M.
        • Seshadri R.
        • Hepp H.
        • Slamon D.J.
        Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer.
        J Natl Cancer Inst. 2003; 95 (PubMed PMID: 12529347): 142-153
        • Dawson S.J.
        • Rueda O.M.
        • Aparicio S.
        • Caldas C.
        A new genome-driven integrated classification of breast cancer and its implications.
        EMBO J. 2013; 32 (PubMed PMID: 23395906; PMCID: PMC3590990): 617-628https://doi.org/10.1038/emboj.2013.19
        • Henderson TO
        • Ness K.K.
        • Cohen H.J.
        Accelerated aging among cancer survivors: from pediatrics to geriatrics.
        Am Soc Clin Oncol Educ Book. 2014; (PubMed PMID: 24857133): e423-e430https://doi.org/10.14694/EdBook_AM.2014.34.e423
        • Berger A.M.
        • Gerber L.H.
        • Mayer D.K.
        Cancer-related fatigue: implications for breast cancer survivors.
        Cancer. 2012; 118 (PubMed PMID: 22488700): 2261-2269https://doi.org/10.1002/cncr.27475
        • Demaria M.
        • O'Leary M.N.
        • Chang J.
        • Shao L.
        • Liu S.
        • Alimirah F.
        • Koenig K.
        • Le C.
        • Mitin N.
        • Deal A.M.
        • Alston S.
        • Academia E.C.
        • Kilmarx S.
        • Valdovinos A.
        • Wang B.
        • de Bruin A.
        • Kennedy B.K.
        • Melov S.
        • Zhou D.
        • Sharpless N.E.
        • Muss H.
        • Campisi J.
        Cellular senescence promotes adverse effects of chemotherapy and cancer relapse.
        Cancer Discov. 2017; 7 (Epub 2016/12/17) (PubMed PMID: 27979832; PMCID: PMC5296251): 165-176
        • Chang J.
        • Wang Y.
        • Shao L.
        • Laberge R.M.
        • Demaria M.
        • Campisi J.
        • Janakiraman K.
        • Sharpless N.E.
        • Ding S.
        • Feng W.
        • Luo Y.
        • Wang X.
        • Aykin-Burns N.
        • Krager K.
        • Ponnappan U.
        • Hauer-Jensen M.
        • Meng A.
        • Zhou D.
        Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice.
        Nat Med. 2016; 22 (Epub 2015/12/15) (PubMed PMID: 26657143; PMCID: PMC4762215): 78-83