Breast cancer risk in premalignant lesions: osteopontin splice variants indicate prognosis

Premalignant breast lesions pose variable risks for transformation, raising the question who should receive treatment to counteract the potential progression to breast cancer. Because the secreted metastasis mediator Osteopontin (OPN) is a marker for breast cancer aggressiveness, its presence in these lesions may reflect progression risk. By immunohistochemistry, we analyse the association of Osteopontin variant expression in healthy breasts, hyperplasias, papillomas, and carcinomas in situ from 434 women to assess a) staining for OPN exon 4 (present in OPN-a and OPN-b) or OPN-c in low-risk to high-risk lesions b) correlations between staining and progression (DCIS with invasion, invasive cancer) or survival. The markers correlate with risk, and they are prognostic for ensuing invasive disease and survival. About 10% of OPN-c pathology score 0–1 (intensity), vs. 40% of score 3 experience cancer over 5 years. More than 90% of women, who progress, had pathology scores of 2–3 for OPN-c intensity at the time of initial diagnosis. When combining OPN-c and OPN exon 4 staining, all of the low intensity patients are alive after 5 years, whereas women in the high category have a close to 30% chance to die within 5 years. Of patients who succumb, close to 80% had a high combined score at the time of initial diagnosis. The combined information of OPN splice variant immunohistochemistry can provide a foundation for very reliable prognostication and has the potential to aid decision making in the treatment of early breast lesions.