Abstract
BackgroundPremalignant 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.MethodsBy 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.ResultsThe 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.ConclusionThe 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.
Highlights
The progress achieved in imaging and detection over recent years has generated a relatively new dilemma in breast disease: Which patients with premalignant lesions should receive treatment to prevent the future development of breast cancer? While such changes are present in about 5% of disease-free women, their clinical significance is uncertain as not all cases progress.[1,2] Women with preinvasive disease have three options, observation, chemoprevention, or surgery
Stages of breast transformation develop from hyperplasia to atypia (flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH)3,4), papillomatosis or lobular carcinoma in situ (LCIS) with moderate risk for transformation
While there is a substantial need in breast cancer progression to identify biomarkers for the sequence: hyperplasia → atypia/ papilloma → ductal carcinoma in situ (DCIS) → DCIS with microinvasion → invasive ductal cancer (IDC), or alternatively from atypia via LCIS to invasive lobular cancer (ILC), current breast histopathology does not allow the reliable diagnosis of this invasive potential
Summary
The progress achieved in imaging and detection over recent years has generated a relatively new dilemma in breast disease: Which patients with premalignant lesions should receive treatment to prevent the future development of breast cancer? While such changes are present in about 5% of disease-free women, their clinical significance is uncertain as not all cases progress.[1,2] Women with preinvasive disease have three options, observation, chemoprevention (mostly with selective estrogen receptor modulators or aromatase inhibitors), or surgery (lumpectomy or mastectomy). The acquisition of invasiveness is a critical step in these early breast carcinomas It is associated with the aberrant expression and splicing of specific tumour progression genes that allow the cells to penetrate the basement membrane.[5] While there is a substantial need in breast cancer progression to identify biomarkers for the sequence: hyperplasia → atypia/ papilloma → DCIS → DCIS with microinvasion → invasive ductal cancer (IDC), or alternatively from atypia via LCIS to invasive lobular cancer (ILC), current breast histopathology does not allow the reliable diagnosis of this invasive potential. METHODS: 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 OPNb) or OPN-c in low-risk to high-risk lesions b) correlations between staining and progression (DCIS with invasion, invasive cancer) or survival. CONCLUSION: 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
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