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Molecular Subtypes of Breast Cancers Detected in Mammography Screening and Outside of Screening

Authors' Affiliations: ¹ Laboratory of Molecular Oncology, Biomedicum; Departments of ² Oncology and ³ Obstetrics and Gynecology, Helsinki University Central Hospital; ⁴ Biomedical Informatics Research Group, Department of Oncology and Folkhälsan Research Center, University of Helsinki; ⁵ Department of Pathology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland; ⁶ Department of Palliative Medicine and Oncology and ⁷ Institute of Medical Technology, Tampere University Hospital, Tampere, Finland; ⁸ Department of Oncology, Vaasa Central Hospital, Vaasa, Finland; ⁹ Department of Oncology, Kuopio University Hospital, Kuopio, Finland; and ¹⁰ Department of Oncology and Radiology, Oulu University Central Hospital, Oulu, Finland

Requests for reprints: Heikki Joensuu, Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 8, P.O. Box 180, FIN-00029 Helsinki, Finland. Phone: 358-9-471-73208; Fax: 358-9-471-74202; E-mail: heikki.joensuu{at}hus.fi.

Purpose: The frequency and significance of gene expression profile-derived molecular subtypes of breast cancers found in mammography screening are unknown.

Experimental Design: We identified breast cancers diagnosed in women of any age living in defined geographic regions in Finland in 1991 to 1992 and collected clinical and pathologic data. Surrogates for the molecular subtypes were determined for 247 cancers found in organized mammography screening and 989 cancers detected outside of screening using immunohistochemistry or in situ hybridization. Molecular subtypes were defined as luminal A [estrogen receptor (ER) positive and/or progesterone receptor (PR) positive, HER2-], luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, cytokeratin 5+, and/or HER1+), HER2+/ER- (ER-, PR-, and HER2+), and unclassified. The median follow-up time was 9.4 years.

Results: The luminal type A was common (73.7%) and the HER2+/ER- type is rare (5.7%) in screen-detected cancer, and only 16% were HER2 positive. Women with cancer diagnosed in screening at ages 50 to 69 years had similar molecular subtype distribution as women whose cancer was found outside of screening at age >69 years. In a multivariate model, cancer detection at screening independently predicted favorable distant disease-free survival when the molecular subtype was included as a covariate in addition to age, histologic grade, and cancer size. Women with small (pT₁N₀M₀) HER2-positive cancer had similar outcome regardless of the method of detection.

Conclusions: Molecular subtype distribution of screen-detected breast cancer differs from that of cancers found outside of screening and accounts in part for the better outcome of screen-detected cancer.

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