Assessment of breast cancer risk factors reveals subtype heterogeneity

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Holm, JohannaKarolinska Institutet (author)

Assessment of breast cancer risk factors reveals subtype heterogeneity

Article/chapterEnglish2017

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Stockholm :Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics,2017
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LIBRIS-ID:oai:openarchive.ki.se:10616/47145
ISSN:0008-5472
10616/47145hdl
http://hdl.handle.net/10616/47145URI
https://doi.org/10.1158/0008-5472.CAN-16-2574DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:136113788URI

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Language:English
Summary in:English

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Subtype heterogeneity for breast cancer risk factors has been suspected, potentially reflecting etiological differences and implicating risk prediction. Reports are conflicting regarding presence of heterogeneity for many exposures. To examine subtype heterogeneity across known breast cancer risk factors, we conducted a case-control analysis of 2,632 breast cancers and 15,945 controls in Sweden. Molecular subtype was predicted from pathology-record derived immunohistochemistry markers by a classifier trained on PAM50 subtyping. Multinomial logistic regression estimated separate odds ratios for each subtype by the exposures parity, age at first birth, breastfeeding, menarche, HRT use, somatotype at age 18, benign breast disease, mammographic density, polygenic risk score, family history of breast cancer and BRCA mutations. We found clear subtype heterogeneity for genetic factors and breastfeeding. The polygenic risk score was associated with risk of all subtypes except for the basal-like (p heterogeneity < 0.0001). Parous women who never breastfed were at higher risk of basal-like subtype (OR 4.17; 95% CI 1.89 to 9.21) compared to both nulliparous (reference) and breastfeeding women. Breastfeeding was not associated with risk of HER2-overexpressing type, but protective for all other subtypes. The observed heterogeneity in risk of distinct breast cancer subtypes for germline variants supports heterogeneity in etiology and has implications for their use in risk prediction. The increased risk of basal-like subtype among women who never breastfed merits more research into potential causal mechanisms and confounders.

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Eriksson, LouiseKarolinska Institutet (author)
Ploner, AlexanderKarolinska Institutet (author)
Eriksson, MikaelKarolinska Institutet (author)
Rantalainen, MattiasKarolinska Institutet (author)
Li, Jingmei (author)
Hall, PerKarolinska Institutet (author)
Czene, KamilaKarolinska Institutet (author)
Karolinska Institutet
Karolinska Institutet
Karolinska Institutet (creator_code:org_t)

Related titles

In:Cancer ResearchStockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics77:13, s. 3708-37170008-5472
In:Cancer researchStockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics77:13, s. 3708-37171538-7445

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By the author/editor: Holm, Johanna; Eriksson, Louise; Ploner, Alexande ...; Eriksson, Mikael; Rantalainen, Mat ...; Li, Jingmei; show more...; Hall, Per; Czene, Kamila; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

NATURAL SCIENCES: NATURAL SCIENCES; and Mathematics; and Probability Theo ...

Articles in the publication: Cancer Research; Cancer research

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