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. 2017 Jul;164(1):107-117.
doi: 10.1007/s10549-017-4222-8. Epub 2017 Mar 31.

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

Jeanne S Mandelblatt  1 , 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
Affiliations

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

Jeanne S Mandelblatt et al. Breast Cancer Res Treat. 2017 Jul.

Abstract

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

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00068328.

Keywords: Breast cancer; Frailty; Mortality; Older; Survival.

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Conflict of interest statement

Conflict of Interest Disclosures: Jeanne S. Mandelblatt, MD, MPH- None

Ling Cai, PhD - None

George Luta, PhD - None

Gretchen Kimmick, MD - Consultant to Genomic Health, AstraZeneca, Novartis, Pfizer

Jonathan Clapp, MS- None

Claudine Isaacs, MD - Honoraria from Genentech and Pfizer; Advisory board for Astra-Zeneca

Brandelyn Pitcher, MS- None

William Barry, PhD - None

Eric Winer, MD – None

Steve Sugarman – None

Clifford Hudis, MD - None

Hyman Muss, MD - None

Harvey J. Cohen, MD- None

Arti Hurria, MD- Consulting services for Boehringer Ingelheim, Carevive, Sanofi, GTx Inc, and Perian Biosciences and research funding from Novartis, Celegene, and GSK.

Figures

Figure 1
Figure 1. Study Sample of Older Patients with Newly Diagnosed, Non-Metastatic Breast Cancer Followed for Vital Status for up to 7 years
Legend for Figure 1. The figure provides the study schema for enrollment and analysis. Note: compared to an earlier report from this cohort that included 1529 eligible and 1288 patients , one participant was found later to be ineligible and 8 women subsequently withdrew consent. The final cohort in the locked dataset included 1280 patients. Among the 15 patients with missing frailty data (1.2%), 12 were alive at last known follow-up and 3 died of breast cancer.
Figure 2a
Figure 2a. Unadjusted Cumulative Incidence Rates of All-Cause Mortality among Older Breast Cancer Patients by Frailty Category for up to Seven Years of Follow-up
Figure 2b
Figure 2b. Unadjusted Cumulative Incidence Rates of Breast Cancer Mortality among Older Breast Cancer Patients by Frailty Category for up to Seven Years of Follow-up
Legend for Figure 2. Mortality Outcomes by Frailty Category Among Older Breast Cancer Patients with up to Seven Years of Follow-up. The top panel shows all-cause mortality; the bottom panel shows breast cancer-specific mortality. Unadjusted rates of all-cause mortality are from Kaplan-Meier analyses; rates of breast cancer specific mortality are from a univariable competing risk model. P-values for differences in frailty based on log-rank tests or Gray's tests, respectively. P-values for differences in mortality outcome by frailty group in both panels are <0.001. In each panel, the dot-dash line indicates patients in the frail category; the dotted line indicates the pre-frail category; the dashed line indicates the robust category of patients; and the solid line indicates the overall cohort.
See this image and copyright information in PMC

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