Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands

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Abstract

Objective

To investigate the incidence and characteristics of breast cancer in transgender people in the Netherlands compared with the general Dutch population.

Design

Retrospective, nationwide cohort study.

Setting

Specialised tertiary gender clinic in Amsterdam, the Netherlands.

Participants

2260 adult trans women (male sex assigned at birth, female gender identity) and 1229 adult trans men (female sex assigned at birth, male gender identity) who received gender affirming hormone treatment.

Main outcome measures

Incidence and characteristics (eg, histology, hormone receptor status) of breast cancer in transgender people.

Results

The total person time in this cohort was 33 991 years for trans women and 14 883 years for trans men. In the 2260 trans women in the cohort, 15 cases of invasive breast cancer were identified (median duration of hormone treatment 18 years, range 7-37 years). This was 46-fold higher than in cisgender men (standardised incidence ratio 46.7, 95% confidence interval 27.2 to 75.4) but lower than in cisgender women (0.3, 0.2 to 0.4). Most tumours were of ductal origin and oestrogen and progesterone receptor positive, and 8.3% were human epidermal growth factor 2 (HER2) positive. In 1229 trans men, four cases of invasive breast cancer were identified (median duration of hormone treatment 15 years, range 2-17 years). This was lower than expected compared with cisgender women (standardised incidence ratio 0.2, 95% confidence interval 0.1 to 0.5).

Conclusions

This study showed an increased risk of breast cancer in trans women compared with cisgender men, and a lower risk in trans men compared with cisgender women. In trans women, the risk of breast cancer increased during a relatively short duration of hormone treatment and the characteristics of the breast cancer resembled a more female pattern. These results suggest that breast cancer screening guidelines for cisgender people are sufficient for transgender people using hormone treatment.

Related collections

Most cited references 28

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Breast cancer and hormone-replacement therapy in the Million Women Study.

Valerie Beral (2003)

Current use of hormone-replacement therapy (HRT) increases the incidence of breast cancer. The Million Women Study was set up to investigate the effects of specific types of HRT on incident and fatal breast cancer. 1084110 UK women aged 50-64 years were recruited into the Million Women Study between 1996 and 2001, provided information about their use of HRT and other personal details, and were followed up for cancer incidence and death. Half the women had used HRT; 9364 incident invasive breast cancers and 637 breast cancer deaths were registered after an average of 2.6 and 4.1 years of follow-up, respectively. Current users of HRT at recruitment were more likely than never users to develop breast cancer (adjusted relative risk 1.66 [95% CI 1.58-1.75], p<0.0001) and die from it (1.22 [1.00-1.48], p=0.05). Past users of HRT were, however, not at an increased risk of incident or fatal disease (1.01 [0.94-1.09] and 1.05 [0.82-1.34], respectively). Incidence was significantly increased for current users of preparations containing oestrogen only (1.30 [1.21-1.40], p<0.0001), oestrogen-progestagen (2.00 [1.88-2.12], p<0.0001), and tibolone (1.45 [1.25-1.68], p<0.0001), but the magnitude of the associated risk was substantially greater for oestrogen-progestagen than for other types of HRT (p<0.0001). Results varied little between specific oestrogens and progestagens or their doses; or between continuous and sequential regimens. The relative risks were significantly increased separately for oral, transdermal, and implanted oestrogen-only formulations (1.32 [1.21-1.45]; 1.24 [1.11-1.39]; and 1.65 [1.26-2.16], respectively; all p<0.0001). In current users of each type of HRT the risk of breast cancer increased with increasing total duration of use. 10 years' use of HRT is estimated to result in five (95% CI 3-7) additional breast cancers per 1000 users of oestrogen-only preparations and 19 (15-23) additional cancers per 1000 users of oestrogen-progestagen combinations. Use of HRT by women aged 50-64 years in the UK over the past decade has resulted in an estimated 20000 extra breast cancers, 15000 associated with oestrogen-progestagen; the extra deaths cannot yet be reliably estimated. Current use of HRT is associated with an increased risk of incident and fatal breast cancer; the effect is substantially greater for oestrogen-progestagen combinations than for other types of HRT.

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Pathology Databanking and Biobanking in The Netherlands, a Central Role for PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive

M. Casparie, A Tiebosch, A Burger … (2007)

Since 1991, a nationwide histopathology and cytopathology network and archive is in operation in The Netherlands under the name PALGA, encompassing all sixty-four pathology laboratories in The Netherlands. The overall system comprises decentralized systems at the participating laboratories, a central databank, and a dedicated communication and information exchange tool. Excerpts of all histopathology and cytopathology reports are generated automatically at the participating laboratories and transferred to the central databank. Both the decentralized systems and the central system perform checks on the quality and completeness of excerpts. Currently, about 42 million records on almost 10 million patients are stored in the central databank. Each excerpt contains patient identifiers, including demographic data and the so-called PALGA diagnosis. The latter is structured along five classification axes: topography, morphology, function, procedure, and diseases. All data transfer and communication occurs electronically with encryption of patient and laboratory identifiers. All excerpts are continuously available to all participating pathology laboratories, thus contributing to the quality of daily patient care. In addition, external parties may obtain permission to use data from the PALGA system, either on an ongoing basis or on the basis of a specific permission. Annually, 40 to 60 applications for permission to use PALGA data are submitted. Among external users are the Dutch cancer registry, population-based screening programs for cancer of the uterine cervix and breast cancer in The Netherlands, and individual investigators addressing a range of research questions. Many scientific papers and theses incorporating PALGA data have been published already. In conclusion, the PALGA system is a unique system that requires a minimal effort on the part of the participating laboratories, while providing them a powerful tool in their daily practices.

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The Amsterdam Cohort of Gender Dysphoria Study (1972–2015): Trends in Prevalence, Treatment, and Regrets

Thomas Steensma, Chantal M. Wiepjes, Nienke M Nota … (2018)

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All references

Author and article information

Contributors

Christel J M de Blok: Role: PhD candidate

Chantal M Wiepjes: Role: PhD candidate

Nienke M Nota: Role: PhD candidate

Klaartje van Engelen: Role: clinical geneticist

Muriel A Adank: Role: clinical geneticist

Koen M A Dreijerink: Role: endocrinologist

Ellis Barbé: Role: pathologist

Inge R H M Konings: Role: medical oncologist

Martin den Heijer:

ORCID: http://orcid.org/0000-0003-3620-5617

Role: professor in endocrinology and head of division

Journal

Journal ID (nlm-ta): BMJ

Journal ID (iso-abbrev): BMJ

Journal ID (publisher-id): BMJ-UK

Journal ID (hwp): bmj

Title: The BMJ

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1756-1833

Publication date Collection: 2019

Publication date (Electronic): 14 May 2019

Volume: 365

Electronic Location Identifier: l1652

Affiliations

[1 ]Centre of Expertise on Gender Dysphoria, Amsterdam UMC, VU University Medical Centre, Amsterdam, Netherlands

[2 ]Department of Endocrinology, Amsterdam UMC, VU University Medical Centre, Amsterdam, Netherlands

[3 ]Department of Clinical Genetics, Amsterdam UMC, VU University Medical Centre, Amsterdam, Netherlands

[4 ]Department of Clinical Genetics, Netherlands Cancer Institute, Amsterdam, Netherlands

[5 ]Department of Pathology, Amsterdam UMC, VU University Medical Centre, Amsterdam, Netherlands

[6 ]Department of Oncology, Amsterdam UMC, VU University Medical Centre, Amsterdam, Netherlands

Author notes

Correspondence to: M den Heijer, Department of Internal Medicine, Section Endocrinology, Amsterdam UMC, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, Netherlands m.denheijer@ 123456vumc.nl

Author information

Martin den Heijer http://orcid.org/0000-0003-3620-5617

Article

Publisher ID: debc047425

DOI: 10.1136/bmj.l1652

PMC ID: 6515308

PubMed ID: 31088823

SO-VID: 4a754642-a560-4469-9b8d-6e156fed08c8

License:

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date accepted : 27 March 2019

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Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands

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Abstract

Objective

Design

Setting

Participants

Main outcome measures

Results

Conclusions

Related collections

Journal of the Netherlands Society of Toxicology

Most cited references 28

Breast cancer and hormone-replacement therapy in the Million Women Study.

Pathology Databanking and Biobanking in The Netherlands, a Central Role for PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive

The Amsterdam Cohort of Gender Dysphoria Study (1972–2015): Trends in Prevalence, Treatment, and Regrets

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