Breast Cancer Risk and Disease Outcomes for Australian Aboriginal Women

Transcription

1 Breast Cancer Risk and Disease Outcomes for Australian Aboriginal Women

2 On the Agenda How frequent is breast cancer in the Indigenous population relative to non- Indigenous people. How do breast cancer outcomes differ between Indigenous and non-indigenous populations and why.

3 Breast Cancer Incidence In Australia by Aboriginal Status

4 Incidence: Age Standardised Rate per 100,000 Breast Cancer Incidence In WA by Aboriginal Status Non-Aboriginal Aboriginal Median ASR: 59 Indigenous v 86 Non-Indigenous. HR 0.69 (Incidences per 100,000) Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

5 Why is Incidence Low? The Aboriginal population age structure is very young. Risk factor profiles between the populations vary.

6 Lower Incidence: Likely A Result of Population Age Structure Age structure of the Australian population, by Indigenous status

7 % of all breast cancers Lower Incidence: Likely A Result of Population Age Structure Breast Cancer In the Young: A Relatively Rare Condition Age Category AIHW Report 2012

8 Why is Incidence Low? The Aboriginal population age structure is very young. Risk factor profiles between the populations vary.

9 Protection Comes at a Price

10 The More the Merrier?

11 Risk Factors By ER Status ER Positive ER Negative Zhang et al. Cancer Epidemiol Biomarkers Prev 2005;14(8): Yang et al. J Natl Cancer Inst 2011;103(3): McDermott et al. Med J Aust 2000;172(10): Li et al. Public Health Nutr 2012;15(10): Australian Bureau of Statistics. National Aboriginal and Torres Strait Islander health survey,

12 Risk Factors By ER Status ER Positive ER Negative Children at an older age Lower rates of parity Less breast feeding Use of HRT Zhang et al. Cancer Epidemiol Biomarkers Prev 2005;14(8): Yang et al. J Natl Cancer Inst 2011;103(3): McDermott et al. Med J Aust 2000;172(10): Li et al. Public Health Nutr 2012;15(10): Australian Bureau of Statistics. National Aboriginal and Torres Strait Islander health survey,

13 Indigenous Parity The birth rate for Indigenous women is relatively high. In 2013, the fertility rate for Indigenous women was 2.3 babies per woman, compared with 1.9 for all women. This, however is a fall from 4.55 per Indigenous woman in 1981.

14 ER Negative Breast Cancer Risk

15 Risk Factors By ER Status ER Positive ER Negative Lower socioeconomic status Folate deficiency Increased alcohol intake Obesity Zhang et al. Cancer Epidemiol Biomarkers Prev 2005;14(8): Yang et al. J Natl Cancer Inst 2011;103(3): McDermott et al. Med J Aust 2000;172(10): Li et al. Public Health Nutr 2012;15(10): Australian Bureau of Statistics. National Aboriginal and Torres Strait Islander health survey,

16 On the Agenda How frequent is breast cancer in the Indigenous population relative to non- Indigenous people. How do breast cancer outcomes differ between Indigenous and non-indigenous populations and why.

17 Breast Cancer-Specific Survivals: Indigenous Women

18 Indigenous Australia Breast Cancer-Specific Survivals: Indigenous Women International comparison of mortality-to-incidence ratios for breast cancer, 2008

19 Survivals for Indigenous Women: State by State State Year Author Period N 5yr cancer mortality % Risk Cancer Mortality Corrections Sig/CI NT 2005 Condon NSW 2012 Morrell QLD 2012 Dasgupta SA 2010 Chong All 2012 Roder

20 Survivals for Indigenous Women: State by State State Year Author Period N 5yr cancer mortality % Risk Cancer Mortality Corrections Sig/CI NT 2005 Condon NR NSW 2012 Morrell NR QLD 2012 Dasgupta v 11 SA 2010 Chong v 20 All 2012 Roder v 10

21 Survivals for Indigenous Women: State by State State Year Author Period N 5yr cancer mortality % Risk Cancer Mortality Corrections Sig/CI NT 2005 Condon NR 4.7 nil NSW 2012 Morrell NR 1.54 age,stage QLD 2012 Dasgupta v remoteness, stage <0.001 SA 2010 Chong v nil All 2012 Roder v remoteness, stage, SES, age

22 Overall survival Outcomes for Indigenous Breast Cancer Patients Indigenous-Specific Survival Indigenous outcomes Years After Surgery Chong A, Roder D. Asian Pacific J Cancer Prev. 2010; 11:

23 Poor Outcomes: Possible Explanations Lower screening causing later presentation Higher Co-morbidities Lower acceptance or completion of therapy

24 Indigenous Patients and Screening 52.2% of Indigenous women in screening lived in outer regional or remote areas compared to 13.1% of other women 68% were in the bottom two socioeconomic quartiles compared to 39.8% of other women Participation rate was 36.3% compared to 57.5% over a two year period. Large lesions (>15mm) were moderately more common in Indigenous women 43.4 v 38.5% Mastectomy compared to conservative surgery was also more common 34.8% v 28.2% Roder et al Asian Pacific J Cancer Prev, 13,

25 Poor Outcomes: Possible Explanations Lower screening causing later presentation Higher Co-morbidities Lower acceptance or completion of therapy

26 Treatment Disparities? Valery et al. Lancet 2006, 367(9525):

27 Treatment Disparities? Treatment Modalities Utilised in Non-Metastatic Cancer Therapy: Queensland Moore et al. BMC Cancer Jul 18;14:517.

28 Indigenous Outcomes: A Gap In Knowledge After adjusting for socio-demographic factors, tumour size, nodal spread and time from last screen to diagnosis, Aboriginal and Torres Strait Islander women have approximately twice the risk of death from breast cancer as other women. Roder et al Access to services and socioeconomic factors are unlikely to be the main causes of the early lower Indigenous survival. There is an urgent need to identify the factors leading to poor outcomes early after diagnosis among Indigenous people. Cramb et al

29 Looking for a Way Forward

30 Breast Cancer: Five Diseases In One Adenocarcinoma ER +ive ER -ive Luminal Luminal A Luminal B Basal Normal HER2-Like Triple Negative

31 Overall survival Outcomes for Indigenous Breast Cancer Patients Disease-free survival Indigenous-Specific Survival Subtype-Specific Survival Indigenous outcomes Years After Surgery Months After Surgery Chong A, Roder D. Asian Pacific J Cancer Prev. 2010; 11: Park S et al. Breast. 2012; Feb;21(1): 50-7.

32 Biological Disparity Precedents HER2 +ive Basal Type Italian Sudanese 0 Caucasian Afro-Caribbean Carey LA et al.. JAMA. 2006; 295(21): Awadelkarim KD, et al. Histopathology. 2008; 52:

33 Risk Factors By ER Status ER Positive Children at an older age ER Negative Lower socioeconomic status Lower rates of parity Folate deficiency Less breast feeding Increased alcohol intake Use of HRT Obesity Zhang et al. Cancer Epidemiol Biomarkers Prev 2005;14(8): Yang et al. J Natl Cancer Inst 2011;103(3): McDermott et al. Med J Aust 2000;172(10): Li et al. Public Health Nutr 2012;15(10): Australian Bureau of Statistics. National Aboriginal and Torres Strait Islander health survey,

34 Hypothesis That the unexplained element of the inferior prognosis observed in Aboriginal women with breast cancer is driven by a preponderance of biologically higher risk tumour types, driven by exposure to a different spectrum of risk factors.

35 Study Methods: Overview Retrospective analysis Western Australian women diagnosed with early breast cancer Incidence 2001 to 2010 Data extracted from WA State Cancer Registry & linked pathology reports ER/PR/HER2 expression Histological grade (Bloom and Richardson) Indigenous cases matched (1:3) to non-indigenous cases Matching by age and remoteness Ethics Approved by HRECs of WAAHEC, RPH, DoH and NDU.

36 Breast Cancer Subgroups: Surrogate Assignment Defined by presence or absence of receptors (ER, PR and HER2) with grade as a surrogate for proliferation: Luminal A - ER+ and/or PR+, HER2-, Grade 1-2 Luminal B - ER+ and/or PR+, HER2-, Grade 3 or ER+ and/or PR+, HER2+ HER2-enriched - ER-, PR-, HER2+ Triple negative breast cancer - ER-, PR-, HER2- Park et al. Breast 2012;21(1):50-7.

37 Breast Cancer Incidence In WA by Aboriginal Status 142 patients in the Indigenous cohort 126 patients with a single diagnosis of breast cancer 2 males with breast cancer 12,014 patients in the non-indigenous cohort 11,932 patients with a single diagnosis of breast cancer 82 males with breast cancer Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

38 Study Cohorts By Age and Remoteness Comparison variable Indigenous (n = 114) Non-Indigenous (n = 314) Age (mean years) ARIA Major Cities Inner Regional Outer Regional Remote Very Remote 30 (26%) 23 (20%) 9 ( 8%) 2 ( 2%) 50 (44%) (24%) (17%) ( 5%) (17%) (36%) Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

39 Study Cohorts - Tumour Features Comparison variable Indigenous (n = 114) Non-Indigenous (n = 314) Tumour size (mean mm)* p = Histological grade I II III 18 (16) 44 (39) 47 (41%) 98 (31%) 132 (42%) 80 (25%) p = Tumour histology Ductal Lobular Lymph node positive 93 (81%) 6 ( 5%) 253 (80%) 25 ( 8%) p = (38%) 84 (27%) p = ER positive 80 (70%) 246 (78%) p = PR positive 70 (61%) 208 (66%) p = HER2 positive 16 (14%) 34 (11%) p = Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

40 Study Cohorts By Biological Subtype ariable Comparison Comparison variable Indigenous variable (n = 114) Tumour subtypes Luminal A Luminal B HER2 TNBC Indigenous Indigenous (n = 114) (n = 114) 50 (50%) 24 (24%) 11 (11%) 15 (15%) Non-Indigenous Non-Indigenous (n = 314) (n = (n 314) = 314) 166 (60%) 48 (18%) 15 ( 5%) 47 (17%) Χ df 3 p = Surgical type 51 (45%) 116 (37%) Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

41 Overall Survival by Aboriginal Status P< (chi2) Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

42 Survival by Aboriginal Status Uni- & Multivariate Assessment of Prognostic Variables for BCSS Prognostic Factor and variable N HR 95% CI P value Indigenous Status (non-indigenous as base comparison) Indigenous unadjusted <0.001 Indigenous - size & age Indigenous - LN, age Indigenous - size, LN, age Indigenous size, LN,age, bio Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

43 Breast Cancer Specific Survival Breast Cancer-Specific Survival by Indigenous status for; a) luminal A, b) luminal B, c) Her2 positive, and d) triple negative cancers a) b) P= (chi2) P=0.04 (chi2) c) d) P=0.08 (chi2) P=0.001 (chi2) Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

44 Survival by Biological Subtype Subtype Five year survival Relative 5 year survival mortality year Indigenous Luminal A vs Non Luminal A subtypes Non Indigenous Luminal A* 78% 97% 80% Non Luminal A* 70% 91% 77% Breakdown of non Luminal A subtypes Luminal B* 69% 91% 76% HER2Enriched 82% 86% 95% TNBC* 63% 93% 68% * p<0.05 using the logrank test 7.3 x 3.3 x 3.4 x 1.3 x 5.3 x Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

45 Overall Survival Survival by Remoteness Years from Diagnosis Source: W.A. Cancer Registry - Health Data Collections, Dept of Health (WA) July 2012.

46 Not the Answer: Other Theories Treatment Disparities Deeper Biology

47 Biological Disparities: Finding the Wolves

48 Biological Disparities? Oncotype Dx Paik et al. JCO 2006; 24(23): Curtis et al. Nature 2012; 486(7403):

49 Where to from here? Indigenous and Nonindigenous cases Pathology Blocks Prescription Data Case File Review Qualitative Interviews Oncotype Dx Integrated Clusters Anti-estrogen Compliance Prescribed Treatment Lifestyle Factors Concepts & Attitudes Biological Disparity Treatment Disparity Risk Disparity Conceptual Disparity

50 Conclusions The lower incidence of breast cancer in Aboriginal women continues. In contrast survivals also remain poor. There was no significant difference in the distribution of biological sub-types. Within all tumours types but HER2 positive Aboriginal survivals were inferior. Patterns of adjuvant treatment and more complex biological drivers will be studied.

51 Acknowledgements Leanne Pilkington & the BreastScreen WA Aboriginal Reference Group Dr. Eddie Lee Honours Researcher Mr. Tim Threllfal WA State Cancer Registry Prof Max Bulsara Biostatistician Prof Jenett Harvey Histopathologist Dr. Douglas Cordell Indigenous Researcher

52