Multiple Primary Cancers in Patients with Breast and Skin Cancer Isabelle Soerjomataram Multiple Primary Cancers in Patients with Breast and Skin Cancer © Isabelle Soerjomataram, 2007 No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photocopying, recording or otherwise, without permission of the author. Several chapters are based on published papers, reproduced with permission of the co-authors and the publishers. Copyright of these papers remains with the publishers. ISBN: 978-90-9022497-8 Cover design by: Robert Erlebach-Fuchs Layout by: Mauricio Avendano Pabon Printed by: Optima Grafische Communicatie, Rotterdam Financial support for the printing of this thesis was provided by the Department of Public Health -Erasmus MC, Comprehensive Cancer Centre South, Novartis Pharma B.V., Amoena Nederland B.V., Eli Lilly Nederland B.V., AstraZeneca B.V. Multiple Primary Cancers in Patients with Breast and Skin Cancer Meervoudige tumoren in borst en huidkanker patiënten Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. S.W.J. Lamberts en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op donderdag 20 december 2007 om 09.00 uur door Isabelle Soerjomataram geboren te Innsbruck, Oostenrijk Promotiecommissie Promotor: Prof.dr. J.W.W . Coebergh Overige leden: Prof.dr. H.A.M. Neumann Prof.dr. J.G.M. Klijn Prof.dr. F.E. van Leeuwen Copromotor: Dr. W.J. Louwman Untuk mama, papa, Colette dan Pandji Y para ti Contents Part I Introduction Chapter 1. Introduction 11 Chapter 2: Epidemiology of multiple primary cancers 19 Part II The epidemiology of breast cancer Chapter 3. On the avoidability of breast cancer in industrialized societies: older 43 mean age at first birth as an indicator of excess breast cancer risk Chapter 4. Does the decrease in hormone-replacement therapy also affect 55 breast cancer risk in the Netherlands? Chapter 5. An overview of prognostic factors for long-term survivors of breast cancer 59 Part III Risk of second primary cancer in breast cancer patients Chapter 6. Rising incidence of breast cancer among female cancer survivors: Implications for surveillance 93 Chapter 7. Primary malignancy after primary female breast cancer in the 103 south of the Netherlands, 1972-2001 Chapter 8. Increased risk of second malignancies after in situ breast 113 carcinoma in a population-based registry Chapter 9. Risks of second primary breast and urogenital cancer following 125 female breast cancer in the south of the Netherlands, 1972-2001 Part IV Risk of second primary cancer in skin cancer patients Chapter 10. A cohort of skin cancer patients: a source for aetiological 141 studies Chapter 11. Are patients with skin cancer at lower risk of developing colorectal 149 or breast cancer? Chapter 12. Decreased risk of prostate cancer after skin cancer diagnosis: 165 A protective role of ultraviolet radiation? Part V General discussion and conclusion Chapter 13. Discussion and conclusion 179 Summary 191 Samenvatting 197 Dankwoord/Acknowledgements 203 Curriculum Vitae 207 List of publications 209 7 PART I Introduction Chapter 1 Introduction Chapter 1 1.1. Multiple primary cancers The extent of the problem The number of cancer survivors has been increasing dramatically and is expected to keep growing in the near future. In the Netherlands, a 38% increase of cancer survivors is estimated from 2005 to 2015, representing an increase from 500,000 to 692,000 (ex-) patients in this period.1 It is well known that individuals who suffered from cancer exhibit a 20% higher risk of subsequent primary malignancies.2 Thus, as the number of cancer survivors increases, the number of patients with multiple primary cancers will increase as well. Because cancer is more frequent among the elderly, the ageing of the Dutch population will cause a further increase in the number of cases with multiple cancers: Only 5%-12% of cancer patients aged 50-64 were previously diagnosed with cancer, versus 12%-26% of those aged over 803. Other forces, including increased awareness of (second) malignancies, the higher use and sensitivity of diagnostic/detection methods, and the recent improvements in cancer treatment and survival will further lead to higher prevalence of multiple cancers. Cancer survivors who develop a second malignancy have a higher risk of dying4 and experience a worsening in their quality of life. Thus, increased interest in second cancer from the epidemiological and clinical perspective is highly relevant. Breast cancer The incidence of breast cancer among women has increased by 50% during the last 30 years. On the other hand, data from the Eindhoven cancer registry in the southwest of the Netherlands indicate that breast cancer mortality has been decreasing by 2% every year since 19955 due to earlier diagnosis and better treatment. These trends have led to a marked increase in the number of female cancer survivors who are at risk of developing another primary cancer. Breast cancer has been the most prevalent malignancy in women,6 and also the most commonly occurring multiple malignancy.7 Of all prevalent malignancies among women, 25% of them are breast cancer.7 Women with breast cancer do not only have an increased risk of second breast cancer. Studies indicate that these women also have an increased risk of developing other female genital, oesophageal, salivary gland and soft tissue cancers. On the other hand, women with a breast cancer have a lower risk compared to the general population, of developing cancer of the cervix, pancreas, lung, non-Hodgkin Lymphoma and chronic lymphocytic leukaemia8. Skin cancer In industrialized countries, we have witnessed an increasing trend in the incidence of skin cancer over the last few decades.9, 10 In 2005, there were 18,715 cases of newly diagnosed basal cell carcinoma (BCC) of the skin, 4,212 cases of squamous cell carcinoma (SCC) of the skin, and 3042 cases of cutaneous melanoma (CM) in the Netherlands11, corresponding to 19%, 4% and 3% of the total number of incident cancers, respectively.3 Due to the low case-specific mortality rates of skin cancer, the prevalence of skin cancer has increased dramatically, providing opportunities for the analysis on the incidence of multiple cancers (see chapter 10 of this thesis). 12 Introduction Recent studies have shown that although sun exposure increases the risk of skin cancer, it may have a protective effect against some major cancers including that of the breast as well as colorectal and prostate cancer, through the formation of vitamin D.12-14 Patients with skin cancer constitute a good cohort to indirectly test this hypothesis. Examining the risk of second cancer among skin cancer patients can provide clues in this paradoxical effect of sun exposure: If more exposure to sunlight increases the risk of skin cancer but reduces the risk of breast, prostate and colorectal cancer, skin cancer patients should have a lower incidence of these cancers compared to the general population. Although cancer registry data do not provide individual information on sun exposure, examining the risk of a second cancer by various host and tumour characteristics may give further idea on the protective role of sun exposure (table 1.1). It is known that cumulative sun exposure is associated with an increased risk of SCC. The association of sun exposure is less strong for BCC, which has been hypothesized to be etiologically more similar to melanoma. Therefore a cohort of patients with SCC should show the highest protective effect against breast, prostate and colorectal cancer and cohort of patients with CM the lowest. Similarly, skin cancers occurring in the head and neck region and those diagnosed at older age are usually associated with chronic exposure and thus a lower risk of second breast, prostate and colorectal cancer skin cancers is expected in this group of patients. Table 1.1. Associations between sun exposure pattern and skin cancer features9, 15 Host and tumour feature Sun Exposure Intermittent Chronic Skin cancer type Squamous Cell Carcinoma + +++ Basal Cell Carcinoma ++ ++ Melanoma +++ + Age at diagnosis Young +++ + Old + +++ Subsite Head and neck + +++ Trunk and extremities +++ + In order to interpret the risk pattern of multiple cancers it is necessary to identify the factors that influence an individual’s risk of developing a second cancer including: internal factors, e.g., genetic predisposition towards cancer; and external factors, e.g., lifestyle, treatment of the first cancer. Hereditary genetic predispositions may increase an individual risk of multiple malignancies.16 Genetic factors have been more commonly related to an increased risk among those who were diagnosed with a first cancer at an early age. Other factors such as lifestyle should influence mainly the risk of second malignancy among the older age groups because of the long exposure time that is needed until such factors cause carcinogenic changes in a human body. Treatment of a first cancer may also be related to the occurrence of a second cancer. Comparing a group of patients who were exposed to a certain treatment to those who were spared from the treatment may further give light on this issue. Furthermore, increased monitoring may also elevate the risk of a second primary cancer. Because the above mentioned factors have changed over time (except for genetic disorders), the risk of a second cancer among cancer patients also changes, thus continuous monitoring of second cancer risk is of utmost importance. Study of multiple cancers will provide information on the necessary guidelines to follow-up cancer patients. 13 Chapter 1 Through such studies the patient group at high risk of developing a second cancer can be identified. In addition, the type of the second cancer with the highest risk and length of time where such risk is increased can be determined.