Prognosis of Patients With Breast Cancer: Causes of Death and Effects of Time Since Diagnosis, Age, and Tumor Characteristics

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1 Prognosis of Patients With Breast Cancer: Causes of Death and Effects of Time Since Diagnosis, Age, and Tumor Characteristics Edoardo Colzani, M.D., M.P.H. Department of Medical Epidemiology and Biostatistics Karolinska Institutet 1 Breast cancer Most common cancer in the female population (30% of all malignant tumors among Swedish women) and second after lung cancer for mortality Five years survival: about 87.5% Carcinoma in situ: about 7% Common subtypes: ductal carcinoma (80%), lobular carcinoma (10-15%) 15%) Prognostic markers: TNM stage, ER status (60% ER+), PR status, HER2/neu status (overexpressed in 20-30% tumors) Breast cancer in the last few decades: what happened in the meanwhile? Change in the prevalence of risk factors mainly due to a change in lifestyle and to the improving wealth: Fewer pregnancies; Change in reproductive life span; Change in body shape; Use of hormone treatments; Screening and early detection Improved breast cancer treatment 3

2 Breast cancer in the last few decades Increasing survival Increasing incidence Increasing prevalence More women alive after treatment for breast cancer what happens to them? 4 Suspected long-term adverse health effects of treatment for breast cancer Surgery Radiotherapy Second primary tumors (lung cancer) Cardiovascular disease Chemotherapy Cardiovascular disease Dementia Second primary tumors Hormone therapy (tamoxifen) Bone fractures Second primary tumors (endometrial cancer) Cardiovascular disease General aim To improve knowledge about long-term prognosis of women diagnosed with breast cancer according to specific patient and tumor characteristics

3 Stockholm Breast Cancer Registry The Stockholm Breast Cancer Registry (SBCR) is a population- based registry held by the Oncological Centre of Stockholm, Sweden It was started in 1976 in the Swedish counties of Stockholm and Gotland The SBCR Collects detailed information about all breast cancers ( patients) diagnosed in the two counties It has 99% completeness for women aged less than 75 years at diagnosis. This proportion decreases to about 80-85% 85% for women aged 75 years or more at diagnosis 7 Prognosis of breast cancer patients Study design: cohort study Study population: 12,850 women diagnosed with first invasive breast cancer (and no history of previous invasive tumors) in the area of Stockholm and Gotland between 1990 and 2006 Exclusions: stage IV (n=238), tumor size <1mm (n=52), neo-adjuvant treatment (n=803), no surgery (n=245) Sources: Stockholm Breast Cancer Registry Swedish National Cause of Death Registry Swedish National Cancer Registry Analysis: survival analysis Flexible parametric models 8 Prognosis of breast cancer patients Outcome: major causes of death Any cause; Death due to breast cancer; Death due to other cancers; Death due to circulatory system disorders; Death due to other causes; Covariates: Age (<44, 45-54, 55-64, 65-74); Adjuvant treatment combinations (none, RT, CT, HT, RT+HT, RT+CT, CT+HT, RT+CT+HT); Calendar period ( , , ); Tumor characteristics: Number of positive lymph nodes (0, 1-3, 4+); status (ER+/-); Tumor size (1-20mm, >20mm). 9

4 Distribution of causes of death within 10 years since BC diagnosis Pe 0.2. ercentage < Age at diagnosis/entry, 4cat Breast cancer Circulatory Other Cancer Other death 10 Death due to any cause by age group Mortality rate (per 1000 person-yrs) Time since diagnosis (yrs) 31/10/11 < Death due to breast cancer Death due to CV disorders Death due to other cancer Death due to any other cause 31/10/11

5 31/10/11

6 Adjusted time-dependent HRs of dying from breast cancer according to node status over follow-up time (a) All ages (<75 yrs) Hazard ra atio Adjusted time-dependent HRs of dying from breast cancer according to status over follow-up time (b) All ages (<75 yrs) 1 17 Adjusted time-dependent HRs of dying from breast cancer according to tumor size over follow-up time (c) All ages (<75 yrs)

7 (a) All ages (<75 yrs) (b) Age <45 yrs (c) Age yrs (d) Age yrs (e) Age yrs (f) All ages (<75 yrs) (g) Age <45 yrs (h) Age yrs (i) Age yrs (j) Age yrs (k) All ages (<75 yrs) (l) Age <45 yrs (m) Age yrs (n) Age yrs (o) Age yrs Conclusions More clinical attention to circulatory system diseases could be paid during the follow-up of breast cancer patients given the increasing proportion of cardiovascular events over time and age Lymph node status is a long-term prognosticator for mortality in breast cancer patients. Early detection profoundly impacts prognosis of breast cancer patients 20 Conclusions The nature of the relationship between status and mortality after 5 years of follow-up should be thoroughly investigated, particularly with respect to the role of hormonal treatment The detrimental effect on prognosis of having a tumor larger than 20mm lasts for more than five years although it gradually decreases with time since diagnosis No particular modifications of effect of tumor characteristics on breast cancer mortality were seen in different age groups

8 Distant metastases in breast cancer patients: time-dependent effects Aims Influence of patient and tumor characteristics on metastasis site and on time to metastasis Influence of metastasis site and time to metastasis on prognosis Molecular markers that predict metastasis site and time to metastasis (future study) 22

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