There is evidence that breast cancer incidence may be significantly reduced in high-risk cohorts by treatment with tamoxifen, prophylactic mastectomy, or prophylactic surgery (1
). However, these risk-reduction strategies carry potential side effects, and prophylactic surgery is expensive. There remains a need for biomarkers to accurately predict short-term risk and identify women most likely to benefit from prevention. Biomarkers that vary with risk and response to prevention interventions are referred to as “surrogate end point biomarkers” (5
). As outlined by Fabian et al., surrogate end point biomarkers should be (a
) biologically and statistically significantly associated with cancer development, (b
) present in a reasonable proportion of at-risk individuals, (c
) obtainable by minimally invasive procedures, and (c
) reversible with prevention interventions that have been validated to decrease cancer incidence (6
). Many modalities have been suggested as potential surrogate end point biomarkers for breast cancer, including mammographic density, serum biomarkers, and breast tissue biomarkers (7
). Currently, there is no consensus as to the optimal surrogate end point biomarker.
Breast tissue biomarkers offer the advantage of directly testing for pre – cancerous changes in the breast. Atypia and lobular carcinoma in situ
are associated with increased breast cancer risk (11
). Moreover, breast cancer incidence in women with atypical hyperplasia or lobular carcinoma in situ
is substantially reduced after treatment with tamoxifen (1
). However, the optimal method to repeatedly sample breast tissue remains controversial. Repeated random core needle biopsies for risk surveillance and/or for measurement of response to a prevention intervention are problematic because, unless the biopsy specimens are obtained from mammographically dense areas, the biopsy is likely to contain few terminal ductal-lobule units (12
). Nipple aspirates have shown some promise, but approximately 40% of nipple aspirates are acellular (13
Random periareolar fine needle aspiration (RPFNA) is a research technique that was developed to assess short-term breast cancer risk in women at high risk of breast cancer (6
). RPFNA has the advantage of being inexpensive and may be performed repeatedly, and the majority of samples are cellular in high-risk premenopausal and perimenopausal women (15
). In a single institution study, cytologic atypia in RPFNA predicted a 5.6-fold independent increase in breast cancer risk in high-risk women (6
). This observation supports the use of cytologic atypia in RPFNA as a marker for high-risk benign lesions in high-risk women.
Although RPFNA has gained acceptance (6
), several issues limit its use: (a
) the reproducibility of RPFNA has not been determined, and (b
) RPFNA has the potential to be operator-dependent. To address these potential limitations, the Cancer and Leukemia Group B (CALGB) Prevention Group tested the reproducibility of RPFNA in a multi-institutional cross-sectional study of high-risk women.
The purpose of our study was to determine the agreement between two Masood Cytology Index scores and two cell count measurements from RPFNA samples of individual women. From July 1, 2007 to June 30, 2008, we prospectively tested the reproducibility of duplicate RPFNA samples from 63 high-risk women. RPFNA was performed on the same breast, on the same day, by the same investigator, using separate needles for sequential aspirations.