Breast Cancer Research and Treatment

, Volume 164, Issue 1, pp 107–117 | Cite as

Frailty and long-term mortality of older breast cancer patients: CALGB 369901 (Alliance)

  • Jeanne S. MandelblattEmail author
  • Ling Cai
  • George Luta
  • Gretchen Kimmick
  • Jonathan Clapp
  • Claudine Isaacs
  • Brandeyln Pitcher
  • William Barry
  • Eric Winer
  • Stephen Sugarman
  • Clifford Hudis
  • Hyman Muss
  • Harvey J. Cohen
  • Arti Hurria



Breast cancer patients aged 65+ (“older”) vary in frailty status. We tested whether a deficits accumulation frailty index predicted long-term mortality.


Older patients (n = 1280) with non-metastatic, invasive breast cancer were recruited from 78 Alliance sites from 2004 to 2011, with follow-up to 2015. Frailty categories (robust, pre-frail, and frail) were based on 35 baseline illness and function items. Cox proportional hazards and competing risk models were used to calculate all-cause and breast cancer-specific mortality for up to 7 years, respectively. Potential covariates included demographic, psychosocial, and clinical factors, diagnosis year, and care setting.


Patients were 65–91 years old. Most (76.6%) were robust; 18.3% were pre-frail, and 5.1% frail. Robust patients tended to receive more chemotherapy ± hormonal therapy (vs. hormonal) than pre-frail or frail patients (45% vs. 37 and 36%, p = 0.06), and had the highest adherence to hormonal therapy. The adjusted hazard ratios for all-cause mortality (n = 209 deaths) were 1.7 (95% CI 1.2–2.4) and 2.4 (95% CI 1.5–4.0) for pre-frail and frail versus robust women, respectively, with an absolute mortality difference of 23.5%. The adjusted hazard of breast cancer death (n−99) was 3.1 (95% CI 1.6–5.8) times higher for frail versus robust patients (absolute difference of 14%). Treatment differences did not account for the relationships between frailty and mortality.


Most older breast cancer patients are robust and could consider chemotherapy where otherwise indicated. Patients who are frail or pre-frail have elevated long-term all-cause and breast cancer mortality. Frailty indices could be useful for treatment decision-making and care planning with older patients.


Older Breast cancer Frailty Survival Mortality 



Dr. Hudis is presently CEO, American Society for Clinical Oncology. This research was conducted while Dr. Hudis was at Memorial Sloan Kettering Cancer Center and does not reflect the views of the American Society for Clinical Oncology. This research was conducted under Alliance for Clinical Trials in Oncology (formerly Cancer and Leukemia Group B) Protocol #369901. This research was supported by the National Cancer Institute at the National Institutes of Health under the Award Number UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), U10CA031946, U10C0A33601, U10CA032291, U10CA047559, U10CA047577, U10CA077597, U10CA077651, U10CA180791, U10CA180857, U10CA180867, U10CA180838, and U10CA84131 to the Alliance, and RO1CA127617 to JSM. The research was also supported, in part, by NCI Grants R35CA197289, RO1CA129769, RO1CA124924, and KO5CA96940 to JSM; and the Biostatistics and Bioinformatics Shared Resources at Georgetown-Lombardi Comprehensive Cancer Center funded by the National Cancer Institute at the National Institutes of Health under grant #P30CA51008. Earlier portions of the research were also funded in part by a grant to support patient accrual from Amgen Pharmaceuticals to the CALGB Foundation. The authors acknowledge Dr. Richard Schilsky for his support of this study; the physicians and patients who participated in the research; the clinical research associates who contributed to data collection; and India Stafford-Clarke for manuscript preparation.

Compliance with ethical standards

Conflict of interest

Gretchen Kimmick—Consultant to Genomic Health, AstraZeneca, Novartis, Pfizer. Claudine Isaacs—Honoraria from Genentech and Pfizer; Advisory board for AstraZeneca. Arti Hurria—Consulting services for Boehringer Ingelheim, Carevive, Sanofi, GTx Inc, and Perian Biosciences and research funding from Novartis, Celegene, and GSK. All other authors declares that they have no conflict of interest.

Supplementary material

10549_2017_4222_MOESM1_ESM.docx (126 kb)
Supplementary material 1 (DOCX 126 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Jeanne S. Mandelblatt
    • 1
    Email author
  • Ling Cai
    • 2
  • George Luta
    • 2
  • Gretchen Kimmick
    • 3
  • Jonathan Clapp
    • 2
  • Claudine Isaacs
    • 4
  • Brandeyln Pitcher
    • 5
  • William Barry
    • 6
    • 7
  • Eric Winer
    • 8
  • Stephen Sugarman
    • 9
  • Clifford Hudis
    • 9
  • Hyman Muss
    • 10
  • Harvey J. Cohen
    • 11
  • Arti Hurria
    • 12
  1. 1.Cancer Prevention and Control Program, Department of OncologyMedStar Georgetown University School of Medicine, Lombardi Comprehensive Cancer CenterWashingtonUSA
  2. 2.Department of Biostatistics, Bioinformatics and Biomathematics, MedStar Georgetown University Medical CenterGeorgetown UniversityWashingtonUSA
  3. 3.Division of Oncology, Department of Medicine, Duke Cancer InstituteDuke University Medical CenterDurhamUSA
  4. 4.Breast Cancer Program, Departments of Medicine and OncologyGeorgetown University School of Medicine, Lombardi Comprehensive Cancer CenterWashingtonUSA
  5. 5.Alliance Statistics and Data CenterDuke UniversityDurhamUSA
  6. 6.Department of BiostatisticsDana Farber Cancer InstituteBostonUSA
  7. 7.Alliance Statistics and Data CenterDana Farber Cancer InstituteBostonUSA
  8. 8.Department of MedicineDana-Farber/Partners CancerCareBostonUSA
  9. 9.Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  10. 10.UNC Lineberger Comprehensive Cancer Center and Department of MedicineUniversity of North CarolinaChapel HillUSA
  11. 11.Department of Medicine and Center for the Study of Aging and Human DevelopmentDuke University Medical CenterDurhamUSA
  12. 12.Department of Medical Oncology and Therapeutics ResearchCity of Hope Comprehensive Cancer CenterDuarteUSA

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