Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis

Harindra Jayasekara, Robert J. MacInnis, James A. Chamberlain, Gillian S. Dite, Nicole M. Leoce, James G. Dowty, Adrian Bickerstaffe, Aung Ko Win, Roger L. Milne, Graham G. Giles, Mary Beth Terry, Diana M. Eccles, Melissa C. Southey, John L. Hopper

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Our aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992–1999 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up = 15.7; range = 0.8–21.4, years). We estimated the mortality hazard as a function of time since diagnosis using a flexible parametric survival analysis with ER status a time-dependent covariate. For women with ER-negative tumors compared with those with ER-positive tumors, 5-year mortality was initially higher (p < 0.001), similar if they survived to 5 years (p = 0.4), and lower if they survived to 10 years (p = 0.02). The estimated mortality hazard for ER-negative disease peaked at ~3 years post-diagnosis, thereafter declined with time, and at 7 years post-diagnosis became lower than that for ER-positive disease. This pattern was more pronounced for women diagnosed at younger ages. Mortality was also associated with lymph node count (hazard ratio (HR) per 10 nodes = 2.52 [95% CI:2.11–3.01]) and tumor grade (HR per grade = 1.62 [95% CI:1.34–1.96]). The risk of death following a breast cancer diagnosis differs substantially and qualitatively with diagnosis age, ER status and time survived. For women who survive >7 years, those with ER-negative disease will on average live longer, and more so if younger at diagnosis.

Original languageEnglish
Number of pages11
JournalInternational Journal of Cancer
DOIs
Publication statusAccepted/In press - 16 Feb 2019

Keywords

  • breast cancer
  • cohort study
  • estrogen receptor
  • mortality
  • survival
  • time-dependent effects

Cite this

Jayasekara, H., MacInnis, R. J., Chamberlain, J. A., Dite, G. S., Leoce, N. M., Dowty, J. G., ... Hopper, J. L. (Accepted/In press). Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis. International Journal of Cancer. https://doi.org/10.1002/ijc.32214
Jayasekara, Harindra ; MacInnis, Robert J. ; Chamberlain, James A. ; Dite, Gillian S. ; Leoce, Nicole M. ; Dowty, James G. ; Bickerstaffe, Adrian ; Win, Aung Ko ; Milne, Roger L. ; Giles, Graham G. ; Terry, Mary Beth ; Eccles, Diana M. ; Southey, Melissa C. ; Hopper, John L. / Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis. In: International Journal of Cancer. 2019.
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abstract = "Our aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992–1999 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up = 15.7; range = 0.8–21.4, years). We estimated the mortality hazard as a function of time since diagnosis using a flexible parametric survival analysis with ER status a time-dependent covariate. For women with ER-negative tumors compared with those with ER-positive tumors, 5-year mortality was initially higher (p < 0.001), similar if they survived to 5 years (p = 0.4), and lower if they survived to 10 years (p = 0.02). The estimated mortality hazard for ER-negative disease peaked at ~3 years post-diagnosis, thereafter declined with time, and at 7 years post-diagnosis became lower than that for ER-positive disease. This pattern was more pronounced for women diagnosed at younger ages. Mortality was also associated with lymph node count (hazard ratio (HR) per 10 nodes = 2.52 [95{\%} CI:2.11–3.01]) and tumor grade (HR per grade = 1.62 [95{\%} CI:1.34–1.96]). The risk of death following a breast cancer diagnosis differs substantially and qualitatively with diagnosis age, ER status and time survived. For women who survive >7 years, those with ER-negative disease will on average live longer, and more so if younger at diagnosis.",
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author = "Harindra Jayasekara and MacInnis, {Robert J.} and Chamberlain, {James A.} and Dite, {Gillian S.} and Leoce, {Nicole M.} and Dowty, {James G.} and Adrian Bickerstaffe and Win, {Aung Ko} and Milne, {Roger L.} and Giles, {Graham G.} and Terry, {Mary Beth} and Eccles, {Diana M.} and Southey, {Melissa C.} and Hopper, {John L.}",
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Jayasekara, H, MacInnis, RJ, Chamberlain, JA, Dite, GS, Leoce, NM, Dowty, JG, Bickerstaffe, A, Win, AK, Milne, RL, Giles, GG, Terry, MB, Eccles, DM, Southey, MC & Hopper, JL 2019, 'Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis' International Journal of Cancer. https://doi.org/10.1002/ijc.32214

Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis. / Jayasekara, Harindra; MacInnis, Robert J.; Chamberlain, James A.; Dite, Gillian S.; Leoce, Nicole M.; Dowty, James G.; Bickerstaffe, Adrian; Win, Aung Ko; Milne, Roger L.; Giles, Graham G.; Terry, Mary Beth; Eccles, Diana M.; Southey, Melissa C.; Hopper, John L.

In: International Journal of Cancer, 16.02.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis

AU - Jayasekara, Harindra

AU - MacInnis, Robert J.

AU - Chamberlain, James A.

AU - Dite, Gillian S.

AU - Leoce, Nicole M.

AU - Dowty, James G.

AU - Bickerstaffe, Adrian

AU - Win, Aung Ko

AU - Milne, Roger L.

AU - Giles, Graham G.

AU - Terry, Mary Beth

AU - Eccles, Diana M.

AU - Southey, Melissa C.

AU - Hopper, John L.

PY - 2019/2/16

Y1 - 2019/2/16

N2 - Our aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992–1999 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up = 15.7; range = 0.8–21.4, years). We estimated the mortality hazard as a function of time since diagnosis using a flexible parametric survival analysis with ER status a time-dependent covariate. For women with ER-negative tumors compared with those with ER-positive tumors, 5-year mortality was initially higher (p < 0.001), similar if they survived to 5 years (p = 0.4), and lower if they survived to 10 years (p = 0.02). The estimated mortality hazard for ER-negative disease peaked at ~3 years post-diagnosis, thereafter declined with time, and at 7 years post-diagnosis became lower than that for ER-positive disease. This pattern was more pronounced for women diagnosed at younger ages. Mortality was also associated with lymph node count (hazard ratio (HR) per 10 nodes = 2.52 [95% CI:2.11–3.01]) and tumor grade (HR per grade = 1.62 [95% CI:1.34–1.96]). The risk of death following a breast cancer diagnosis differs substantially and qualitatively with diagnosis age, ER status and time survived. For women who survive >7 years, those with ER-negative disease will on average live longer, and more so if younger at diagnosis.

AB - Our aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992–1999 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up = 15.7; range = 0.8–21.4, years). We estimated the mortality hazard as a function of time since diagnosis using a flexible parametric survival analysis with ER status a time-dependent covariate. For women with ER-negative tumors compared with those with ER-positive tumors, 5-year mortality was initially higher (p < 0.001), similar if they survived to 5 years (p = 0.4), and lower if they survived to 10 years (p = 0.02). The estimated mortality hazard for ER-negative disease peaked at ~3 years post-diagnosis, thereafter declined with time, and at 7 years post-diagnosis became lower than that for ER-positive disease. This pattern was more pronounced for women diagnosed at younger ages. Mortality was also associated with lymph node count (hazard ratio (HR) per 10 nodes = 2.52 [95% CI:2.11–3.01]) and tumor grade (HR per grade = 1.62 [95% CI:1.34–1.96]). The risk of death following a breast cancer diagnosis differs substantially and qualitatively with diagnosis age, ER status and time survived. For women who survive >7 years, those with ER-negative disease will on average live longer, and more so if younger at diagnosis.

KW - breast cancer

KW - cohort study

KW - estrogen receptor

KW - mortality

KW - survival

KW - time-dependent effects

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