Associations between age at diagnosis and chemotherapy dose reductions in women treated for stage I-IIIA breast cancer.
Authors: Bowles Erin Aiello , Bhimani Jenna , O'Connell Kelli , Gallagher Grace B. , Blinder Victoria Susana , Doud Rachael P. , Griggs Jennifer J. , Kolevska Tatjana , Kroenke Candyce , Laurent Cecile , Liu Raymond , Nakata Kanichi G. , Persaud Sonia , Rivera Donna , Roh Janise M. , Wang Peng , Bandera Elisa Victoria , Kushi Lawrence H. , Kantor Elizabeth 
Published: September 2024

99

Background:
Several studies have shown that older women diagnosed with breast cancer and eligible for chemotherapy treatment are more likely to be dose-reduced than younger women; however, most prior studies were limited by small sample sizes and examined relative dose intensity of a single drug. We assessed the association between age at diagnosis with first cycle dose proportion (FCDP) and average relative dose intensity (ARDI) across multiple regimens in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study.
Methods:
This retrospective cohort study included 10,386 women ages 18+ years treated with adjuvant chemotherapy for stage I-IIIA breast cancer at Kaiser Permanente Northern California (KPNC) and Washington (KPWA) between 2004-2019. We examined associations between age at diagnosis with first cycle dose proportion (FCDP, defined as <90% of the guideline-recommended dose, reflecting clinician intent at treatment outset) and average relative dose intensity (ARDI, defined as dose proportion <90% across the course of chemotherapy). We used multivariable-adjusted generalized linear models of the Poisson family with a log link-function and robust standard errors to calculate prevalence ratios (PR) and corresponding 95% confidence intervals (CI). We adjusted for patient and tumor characteristics, with and without adjusting for pre-existing comorbidities.
Results:
The proportion of women with a FCDP <90% ranged from 3% among women ages 18-39 years to 19% among women ages 75+ years. Women ages 75+ years were statistically significantly more likely to have a FCDP <90% and ARDI <90% vs women ages 40-49 years regardless of adjustment for comorbidities (Table).
Conclusions:
Older age at diagnosis is strongly associated with chemotherapy dose reductions relative to guideline recommendations, both at the outset of chemotherapy initiation and across the course of treatment. Understanding implications of dose reductions on chemotoxicities and survival will be particularly important for improving the quality of care and long-term outcomes for older women.

Age at Diagnosis (years)
FCDP <90% Multivariable Adjusted*PR (95% CI)
FCDP <90% Additionally Adjusted* for ComorbiditiesPR (95% CI)
ARDI <90% Multivariable Adjusted*PR (95% CI)
ARDI <90% Additionally Adjusted* for ComorbiditiesPR (95% CI)

18-39
0.81 (0.53-1.23)
0.84 (0.55-1.29)
0.84 (0.68-1.03)
0.85 (0.69-1.04)

40-49
REF
REF
REF
REF

50-64
1.32 (1.08-1.61)
1.29 (1.06-1.59)
1.16 (1.04-1.29)
1.14 (1.02-1.26)

65-74
1.72 (1.36-2.17)
1.65 (1.29-2.10)
1.34 (1.18-1.52)
1.26 (1.11-1.43)

75+
4.90 (3.61-6.65)
4.39 (3.16-6.09)
1.94 (1.61-2.35)
1.75 (1.44-2.13)

p-trend
<0.001
<0.001
<0.001
<0.001

*Adjusted for BMI, stage at diagnosis, year of diagnosis, study site, race/ethnicity, income, body mass index, human epidermal growth factor receptor status, grade, nodal number, estrogen and progesterone receptor status.