Prognostic factors

(1)

Lotte Holm Land 2013

Komorbide brystkræftpatienter – kan de tåle behandling?

Et registerstudie baseret på Danish Breast Cancer Cooperative Group ”

Lotte Holm Land MD, ph.d.

Onkologisk Afd. R. OUH

Kræft og komorbiditet - alle skal have del i de gode resultater 6. Marts 2013

1

(2)

 The impact of comorbidity on breast cancer specific mortality and other cause mortality.

 Comorbidity and its influence outcome after adjuvant treatment for early breast cancer

 The influence of specific comorbid conditions on breast cancer specific mortality and non-breast cancer mortality

Trine Lembrecht Jørgensen 2

(3)

Background

 Breast cancer is the most frequent malignant disease among women in Denmark.

 A total of 4,944 women diagnosed in 2010

Lotte Holm Land 2013 3

(4)

Epidemiology

0 1000 2000 3000 4000 5000 6000

1990 1993 1996 1999 2002 2005 2008 2009 2010

Incidens Dødelighed

(5)

Background

 The incidence of breast cancer as well as other chronic diseases increase with age

(6)

Prognostic factors

 Tumor size and grade

 Lymph node involvement

 Hormone receptor status

 Age at diagnosis

 Surgery

 Adjuvant treatment

 Year of diagnosis

 Comorbiditet?

(7)

Comorbidity

 Reasons that comorbidity could influence on prognosis in breast cancer patients

 Increased mortality due to the comorbid condition

 Delay of diagnosis

 Increased toxicity to treatment

 Suboptimal or no antineoplastic treatment

 Patients willingness and compliance to treatment

 Biological interaction

(8)

Comorbidity

 Guidelines for breast cancer treatment have been developed from randomized clinical trials (RCT)

 Older patients and patients with comorbidity are excluded from RCTs *

 Studies suggest that older patients without comorbidity have similar beneficial effect of guideline therapy as patients > 70 years**

 Majority of studies reported the influence of comorbidity on death from all causes

 Breast cancer deaths, reflects breast cancer treatment

 Death from other causes is more likely to be caused by comorbid condition

* Bouchardy et al. JCO 2007. Muss et al. NEJM 2009

**Houterman et al. Br J Cancer 2004

(9)

Methods

Databases, Registries & Comorbidity index

 The Danish Breast Cancer Cooperative Group

 The Danish National patient Registry

 The Danish Civil Registration system

 The Danish Register of Causes of Death

 The Charlson Comorbidity Index

(10)

Study cohort

 62,591 women diagnosed with early stage breast cancer in the period 1990-2008, with information on causes of death

 Median potential follow-up 8.2 years

 36% died. (22,282).

16,316 (73%) died of breast cancer and 5,966 (27%) died of other causes.

(11)

Results

5- year OS (%) according to time periods and CCI score

5 year overall survival according to time periods (%) with 95% confidence intervals

Charlson Comorbidity Score

Diagnostic periods. 0 1 2 3+

1990 -1994 72.5 (71.7-73.3) 55.8 (52.8-58.6) 53.0 (48.9-56.8) 42.0 (35.8-48.1) 1995-1999 77.3 (76.6-78.1) 61.5 (58.9-63.9) 56.9 (53.5-60.3) 44.7 (39.9-49.5) 2000-2004 81.6 (80.9-82.2) 68.0 (65.9-69.9) 62.6 (59.8-65.3) 43.5 (39.8-47.0)

(12)

Results

Multivariate analysis with Hazard Ratio and 95% Confidence Intervals

Variable Adjusted HR 95 % CI

Breast Cancer

Specific Mortality CCI O CCI 1 CCI 2 CCI 3+

Reference.

1.30 1.31 1.79

Reference 1.24 – 1.37

1.23 – 1.39 166 – 1.93 Non-Breast Cancer

Mortality CCI 0

CCI 1 CCI 2 CCI 3+

Reference.

1.95 2.15 3.56

Reference 1.82 – 2.09 1.97 – 2.33 3.22 – 3.93 All Cause Mortality CCI 0

CCI 1 CCI 2 CCI 3+

Reference.

1.45 1.52 2.21

Reference 1.40 – 1.51 1.45 – 1.60 2.08 – 2.35

*Adjusted for; age, menopausal status, tumour size, nodal status, deep fascia invasion, vascular invasion, histological type and grade, hormone receptor status, year at diagnosis, type of surgery, and allocated adjuvant treatment.

*all p-values > 0.0001

(13)

Cohort with known adjuvant treatment

(14)

OS according to inclusion in DBCG treatment programme

(15)

Results

Cumulative breast cancer specific mortality according to type of treatment and CCI score

(16)

Breast cancer specific mortality

(17)

Specific chronic conditions

All women diagnosed with breast cancer 1990- 2008 in Denmark. N= 62,591

Charlson comorbidity score 0, 1, and 2.

N= 60,402

Patients with no comorbidity

(CCI=0).

N=39,943

Patients with severe comorbidity (CCI = 3+)

were excluded.

N= 2,189

Patients with mild to moderate comorbidity (CCI= 1-2).

N= 10,574

(18)

Distribution of comorbid conditions in % for each age category

0 10 20 30 40 50 60

<40 years 40-49

years 50-59

years 60-69

years 70-79

years 80+ years

None DM

Chronic pulmonary disease

Cerebrovascular disease

Previous cancer Dementia

(19)

Distribution of treatment (%) according to specific comorbid conditions

Comorbidity Treatment

None Congestive heart failure

Dementia Previous cancer Chronic pulmonary disease

Connective tissue disease

(-) Low risk 12,481 (25) 99 (13) 21 (7) 266 (16) 476 (22) 233 (21)

Endocrine treatment (E)

11,036 (22) 133 (17) 29 (10) 228 (14) 555 (26) 287 (26)

Chemotherapy +/- E

10,440 (21) 20 (3) 8 (3) 113 (7) 272 (13) 153 (14)

Unknown 15,871 (32) 534 (68) 231 (80) 1,026 (63) 853 (40) 439 (39)

Total 49,828 786 289 1,633 1,987 1,112

(20)

5-year Cumulative mortality in % for specific comorbid conditions

5-year Breast cancer specific mortality in % with 95% CI

5-year Other cause mortality in % with 95% CI

None 18.88 18.51-19.26 3.21 3.05-3.39

Chronic pulmonary disease

23.46 21.45-25.52 11.90 10.37-13.55

Connective tissue disease

23.39 20.64-26.24 9.06 7.24-11.13

Previous cancer 23.75 21.50-26.07 8.23 6.83-9.79

DM 29.26 26.20-32.39 10.73 8.72-12.98

Cerebrovascular disease

29.69 27.28-32.13 14.78 12.93-16.75

Congestive heart failure

33.26 29.62-36.90 21.55 18.44-24.82

Dementia 46.26 39.59-52.65 24.00 18.58-29.82

(21)

Results

Breast cancer specific cumulative mortality (%)

(22)

Conclusions

 Patients with high comorbidity score had no improvement in 5 year overall survival over time

 Comorbidity had a prognostic impact on mortality in terms of breast cancer specific mortality, non-breast cancer mortality and all cause mortality.

(23)

Conclusions

 Patients enrolled in a DBCG treatment programme had an overall survival about twice that of patients not enrolled

 Patients with mild to moderate comorbidity (CCI 1-2) recieving chemotherapy had similar risk of breast cancer deaths compared to patients without comorbidity (CCI 0)

(24)

Conclusions

 Patients with Chronic pulmonary disease and Connective tissue disease, are more likely to have known adjuvant

treatment, whereas patients with Congestive heart failure, Dementia and Any tumor are more likely to have treatment unknown.

 Comorbid conditions such as diabetes and congestive heart failure had an independent influence on breast cancer

mortality, compared to other comorbid conditions.

(25)

Perspectives

How do we provide optimal breast cancer

treatment for the elderly with comorbidity?

(26)

Thanks for your attention!

(27)