Association of hospital and physician case volumes with cardiac monitoring and cardiotoxicity during adjuvant trastuzumab treatment for breast cancer: a retrospective cohort study.
BACKGROUND
Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population.


METHODS
In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003-2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity.


RESULTS
Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient-monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity.


CONCLUSIONS
Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Nicolas J
NJ
Chin-Yee
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Andrew T
AT
Yan
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Alexander
A
Kumachev
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Dennis
D
Ko
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Craig
C
Earle
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
George
G
Tomlinson
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Maureen E
ME
Trudeau
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Murray
M
Krahn
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Monika
M
Krzyzanowska
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Raveen
R
Pal
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Christine
C
Brezden-Masley
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Scott
S
Gavura
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Kelly
K
Lien
University of Toronto (Chin-Yee, Yan, Kumachev, Ko, Tomlinson, Trudeau, Krahn, Brezden-Masley, Chan); St. Michael's Hospital (Yan, Brezden-Masley); Institute for Clinical and Evaluative Sciences (Ko, Earle); Sunnybrook Health Sciences Centre (Ko, Earle, Trudeau, Chan); University Health Network (Tomlinson, Krzyzanowska), Toronto, Ont.; Kingston General Hospital (Pal), Kingston; Cancer Care Ontario (Gavura); Canadian Centre for Applied Research in Cancer Control (Chan), Toronto, Ont.
Kelvin
K
Chan