Excess mortality in postmenopausal high-risk women who only receive adjuvant endocrine therapy for estrogen receptor positive breast cancer.
BACKGROUND
Omission of chemotherapy may affect mortality in postmenopausal high-risk women despite appropriate adjuvant endocrine therapy for estrogen receptor (ER) positive breast cancer. The aim of this study was to determine how all-cause mortality rate in these patients compares to that of the general female population. Furthermore, to identify a subset without excess mortality using clinical and pathological characteristics.


METHODS
From the population-based database of the Danish Breast Cancer Cooperative Group we included 6529 postmenopausal patients with ER positive high-risk breast cancer who in 1996 through 2004 by nationwide guidelines were allocated to five years of tamoxifen, an aromatase inhibitor (AI) or both in sequence. Multivariate categorical and fractional polynomials (MFP) models were used to construct prognostic subsets by clinicopathologic characteristics.


RESULTS
In a multivariate model excess mortality was inversely (p < 0.0001) associated with increasing age at surgery while recurrence-free survival (RFS) was not. Non-adherence to endocrine therapy was associated with excess mortality (p = 0.0008) while treatment with an AI was associated with a less pronounced mortality excess (p = 0.03). A prognostic standard mortality rate (SMR) index (PSI) was built using the regression coefficients obtained in the MFP model, and the same risk factors were used to construct a flowchart algorithm. Both allocated 75% to a group with increased all-cause mortality as compared to the general female population, but the SMR was significantly increased (SMR 1.38; 95% CI 1.16-1.65) in 462 patients who were allocated to low-risk group by the Flowchart algorithm and to a high-risk group by PSI.


CONCLUSIONS
Only one quarter of postmenopausal ER positive breast cancer patients are free of excess mortality when omitting adjuvant chemotherapy. Patients should be informed about importance of adherence to adjuvant endocrine therapy and inclusion of an AI. A PSI may better guide recommendations regarding adjuvant chemotherapy.
Danish Breast Cancer Cooperative Group (DBCG) Secretariat and Statistical Office, Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
Bent
B
Ejlertsen
Maj-Britt
MB
Jensen
Henning T
HT
Mouridsen
D000368:Aged; D000465:Algorithms; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D055118:Medication Adherence; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen