Late cardiac effects of adjuvant chemotherapy in breast cancer survivors treated on Southwest Oncology Group protocol s8897.
OBJECTIVE
The late cardiac effects of adjuvant anthracycline therapy in survivors of early-stage breast cancer have had limited study. Subclinical and clinical cardiac late effects may contribute to added comorbidity over time.


METHODS
We recruited patients treated on Southwest Oncology Group (SWOG) protocol S8897 who had been randomly assigned to adjuvant chemotherapy with or without doxorubicin. Left ventricular ejection fraction (LVEF) was evaluated at 5 to 8 years and 10 to 13 years after treatment randomization. Cardiac risk factors and events were reported by clinicians annually between the two assessments.


RESULTS
A total of 180 breast cancer survivors from a potential sample of 1,176 patients were entered, 163 patients at 5 to 8 years and 17 additional patients at 10 to 13 years, with 93 longitudinal assessments of LVEF. There was no significant difference in the proportion of women with an LVEF less than 50% at 5 to 8 (cyclophosphamide, doxorubicin, and fluorouracil [CAF] v cyclophosphamide, methotrexate, and fluorouracil [CMF]: 5% v 7%; P = .68) or 10 to 13 years (CAF v CMF: 3% v 0%; P = .16); however, in an exploratory analysis, the mean LVEF in the doxorubicin group was statistically significantly lower in the 5- to 8-year sample (64.8% v 61.4%; P = .01) but not in the 10- to 13-year sample. In the longitudinal analysis, there was no significant deterioration in LVEF.


CONCLUSIONS
Women enrolled onto an adjuvant chemotherapy treatment clinical trial for breast cancer were successfully recruited to participate in a research study of the late effects of treatment, although many SWOG institutions and potentially eligible patients chose not to participate. In this selected sample, with up to 13 years of follow-up, exposure to doxorubicin did not increase the likelihood of adverse cardiac effects.
Ganz
Patricia A
PA
School of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, 650 Charles Young Dr South, Room A2-125 CHS, Los Angeles, CA 90095-6900, USA. pganz@ucla.edu
Hussey
Michael A
MA
Moinpour
Carol M
CM
Unger
Joseph M
JM
Hutchins
Laura F
LF
Dakhil
Shaker R
SR
Giguere
Jeffrey K
JK
Goodwin
J Wendall
JW
Martino
Silvana
S
Albain
Kathy S
KS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000139:chemically induced* / Q000188:drug therapy; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015996:Survival Rate; D017741:Survivors; D013629:Tamoxifen / Q000008:administration & dosage; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
D003520:Cyclophosphamide; D004317:Doxorubicin; D005472:Fluorouracil; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen