Utility of Breast Cytology Specimens in the Evaluation of Prognostic/Predictive Factors
Although numerous candidate biological and molecular markers of breast cancer have been identified over the past 2 decades, traditional factors as outlined in categories I and II (slides) remain the most useful indicators of prognosis and therapeutic response. These markers can be reliably evaluated in fine-needle aspiration (FNA) specimens of primary or metastatic breast carcinoma. Indications for their assessment were outlined at the National Cancer Institute Consensus Conference in 1966 (slide).

Comparative studies evaluating prognostic/predictive markers in cytology specimens and corresponding tissue sections have shown excellent concordant results. However, the interlaboratory variability in the sensitivity of detection and evaluation of the scoring system is wide, with a high rate of false-negative results (Rhodes et al. and Allred et al.). Because therapies are now being directed toward individual molecular targets, there is a need for increased standardization of both preanalytical and analytical methods and implementation of external quality assurance programs for optimal therapeutic results.

Finally, the utility of FNA of breast lesions is not limited to evaluation of individual prognostic/predictive factors. FNA has been successfully used in the analysis of gene expression profiles using cDNA microarray technology (Ayers et al.). Such investigational studies are under way and may offer great potential for revolutionizing the prediction of cancer prognoses and responses to therapy using cytologic specimens.

Selected references in addition to those listed in the PowerPoint slides:

1. AJCC Cancer Staging Manual, sixth edition, 2002, Springer.
2. Parker RL, Huntsman DG, Lesack DW, et al. Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. Am J Clin Pathol 2002;117:723-728.
3. Hudock JA, Hanau CA, Christen R, et al. Expression of estrogen and progesterone receptors in cytologic specimens using various fixatives. Diagn Cytopathol 1996;15:78-83.
4. Kuenen-Boumeester V, Timmermans AM, De Bruijn EMCA, et al. Immunocytochemical detection of prognostic markers in breast cancer; technical considerations. Cytopathology 1999;10:308-316.
5. Riera J, Simpson JF, Tamayo R, et al. Use of cultured cells as a control for quantitative immunocytochemical analysis of estrogen receptor in breast cancer. Am J Clin Pathol 1999;111:329-335.
6. Ayers M, Symmans WF, Stec J, et al. Gene expression profiling of fine needle aspirations of breast cancer identifies genes associated with complete pathologic response to neoadjuvant taxol/FAC chemotherapy. Breast Cancer Research and Treat 2002;76(Suppl 1):S64 (Abstract 220).