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Breast Cancer Screening Behaviours and Outcomes in Women with a Family History of Breast and/or

Ovarian Cancer in Ontario

by

Meghan Jane Walker

A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy

Dalla Lana School of Public Health University of Toronto

Copyright by Meghan Jane Walker 2014

ii

Breast Cancer Screening Behaviours and Outcomes in Women

with a Family History of Breast and/or Ovarian Cancer in Ontario

Meghan Jane Walker

Doctor of Philosophy

Dalla Lana School of Public Health

University of Toronto

2014

Abstract

Having a family history of breast and/or ovarian cancer is one of the most important risk factors

for developing breast cancer. It is unknown if the survival benefit from mammography

screening extends to women with a family history, and if prognostic features differ by level of

familial risk. The relationship between perceived breast cancer risk and breast screening has

been widely studied in women with familial risk; however, most studies are cross-sectional,

precluding insight into the directionality of this relationship. The objectives of this thesis were

to: examine the impact of mammography screening and familial risk on diagnoses and

prognostic features of breast cancer and benign breast disease (BBD); and examine the effect of

perceived risk on breast screening. An additional methodological objective was to evaluate the

validity of self-reported mammogram data. The data source for this thesis was the Family

History Study (FHS), a prospective cohort study of women from the Ontario site of the Breast

Cancer Family Registry with a family history of breast/ovarian cancer. Women with high

familial risk were more likely to be diagnosed with breast cancer (OR = 2.84; 95% CI:1.50-

5.38), or BBD (OR = 1.94; 95% CI:1.03-3.66), than women with low/moderate risk. No

significant differences were detected in prognostic features by level of risk; however,

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symptomatic cancers were larger (OR = 9.72; 95% CI:1.01-93.61) and diagnosed at a later stage

(OR = 7.80; 95% CI:1.18-51.50) than screen-detected cancers. In low risk women, women who

perceived their risk as >50% were more likely to have a mammogram (OR = 1.13; 95% CI:0.59-

2.16), and clinical breast examination (CBE (OR = 1.11; 95% CI:0.63-1.95) than women who

perceived their risk as 50%. In moderate/high risk women, women who perceived their risk as

>50% were less likely to have a mammogram (OR = 0.70; 95% CI:0.40-1.20), and CBE (OR =

0.52; 95% CI:0.30-0.91) than women who perceived their risk as 50%. Over 90% of women in

the FHS accurately reported their mammogram use in the previous year. Together, these studies

make an important contribution to understanding the effectiveness and use of breast screening in

women with familial risk.

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For Ernest Sinclair, who instilled in me the importance of education

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Acknowledgements

I am grateful to numerous people who made completion of this thesis possible.

My foremost thanks are owed to my supervisor, Dr. Anna Chiarelli, for her daily guidance,

support, and patience throughout this journey. Anna, I am grateful for your mentorship, and I

look forward to future collaborations in cancer screening.

I would also like to acknowledge my advisory committee, Drs. Julia Knight, and Lucia Mirea,

for their instrumental role in guiding my thesis project, and meticulous review at every stage.

Special thanks are owed to Dr. Mirea for the time she has generously spent working with me to

navigate biostatistical issues.

Many thanks are owed to Drs. Heather Bryant, Jason Pole, Shelley Harris, and Rayjean Hung

for the time they dedicated to the critical review of my thesis, their participation in my

examinations, and thoughtful recommendations to improve the thesis.

I would like to acknowledge Drs. Paul Ritvo, Irene Andrulis, and Frances OMalley, as well as

Gord Glendon, for their valuable contributions as co-authors to the research products of this

thesis. I am also indebted to Nancy Deming for the invaluable organizational support she

provided at Cancer Care Ontario.

I would like to acknowledge the financial support I received, namely the Doctoral Fellowship

from the Canadian Breast Cancer Foundation - Ontario Region, and Open Fellowships from the

University of Toronto. Thanks also go to Cancer Care Ontario for twice awarding me the A.H.

Sellers Travel Award, as well as the International Cancer Screening Network for awarding me a

Junior Investigator Scholarship.

I must thank my parents and sister for their enduring support and encouragement during the past

five years. Thank you to my friends for helping me maintain balance in my life. Thank you to

my fellow PhD students for your contributions and advice. I extend my deepest gratitude to

Philip Eley, for both his technical and emotional support throughout this journey.

Lastly, I am grateful to all of the women who shared their time and experience by participating

in this important study.

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Table of Contents

Abstract ......................................................................................................................................... ii

Acknowledgements....................................................................................................................... v

List of Tables ............................................................................................................................... ix

List of Figures .............................................................................................................................. xi

List of Appendices ...................................................................................................................... xii

List of Abbreviations ................................................................................................................. xiii

Chapter 1 Introduction and Objectives ........................................................................................ 1

1.1 Introduction ..................................................................................................................... 1

1.2 Study Objectives .............................................................................................................. 3

Chapter 2 Background and Literature Review ............................................................................ 5

2.1 Epidemiology of Breast Cancer ....................................................................................... 5

2.1.1 Anatomy ................................................................................................................ 5

2.1.2 Tumor Features ...................................................................................................... 6

2.1.3 Histological Type .................................................................................................. 9

2.1.4 Molecular Factors .................................................................................................. 9

2.1.5 Benign Breast Disease ......................................................................................... 10

2.1.7 Familial Breast Cancer ........................................................................................ 12

2.2 Screening for Breast Cancer .......................................................................................... 16

2.2.1 Evidence for the Effectiveness of Breast Cancer Screening ............................... 16

2.2.2 Potential Harms of Breast Cancer Screening ...................................................... 24

2.2.3 Breast Cancer Screening Recommendations in Canada ...................................... 27

2.2.4 Breast Cancer Screening in Canada .................................................................... 29

2.3 Breast Cancer Screening Use and Predictors of Use ..................................................... 31

2.3.1 Participation in breast cancer screening .............................................................. 31

2.3.2 Familial breast cancer risk and participation in breast cancer screening ............ 34

2.3.3 Behavioural factors and breast cancer screening ................................................. 35

2.3.4 Manuscript 1: Perceived risk and adherence to breast cancer screening guidelines

among women with a familial history of breast cancer: A review of the literature ..... 39

vii

2.4 Summary of Evidence and Rationale for the Current Study ......................................... 66

Chapter 3 Study Methods .......................................................................................................... 70

3.1 Summary of Study Design and Data Source ................................................................. 70

3.2 Study Population and Sample ........................................................................................ 71

3.2.1 Ontario site of the Breast Cancer Family Registry .............................................. 71

3.2.2. Family History Study ...............