Cytomorphology of Fibrocystic Change, High-Risk, and Premalignant Breast Lesions

Masood, Shahla

doi:10.1111/j.1524-4741.1995.tb00242.x

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…To facilitate validation of cytologic and biomarker parameters, improvements in quantitation and automation are desirable. A semiquantitative cytology grading system such as that proposed by Masood [30] and a weighted scoring system for immunocytochemistry analysis such as that utilized by Grizzle [311 may decrease intraobserver variability. However, true quantitation requires image analysis of nuclear morphology and immunocytochemical staining.…”

Section: Discussionmentioning

confidence: 99%

“…Women were generally required to be between the ages of 30 and 60. Our rationale for this age range is that the risk of breast cancer development rises sharply after : 30 [191, and that breast tissue of women over 60 usually contains a large amount of fat which makes it difficult to acquire an adequate number of epithelial cells. However, exceptions were made for high-risk women younger than 30 if they were within ten years of the age at whirh their mother or sister were diagnosed with breast cancer.…”

Section: Methodsmentioning

confidence: 99%

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Identification of a chemoprevention cohort from a population of women at high risk for breast cancer

Fabian¹,

Kamel²,

Zalles³

et al. 1996

J. Cell. Biochem.

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In a prospective pilot study, we performed breast fine needle aspirations (FNAs) on 21 3 high-risk and 30 low-risk women and analyzed these aspirates for cytologic changes and biomarker abnormalities of aneuploidy and overexpressed estrogen receptor (ER), epidermal growth factor receptor (ECFR), p53 and HER-2lneu. High-risk women were those with a first degree relative with breast cancer (73%), prior biopsy indicating premalignant breast disease (26%), a history of breast cancer (1 3%), or some multiple of these risk factors (1 1 %). Median ages of the high-risk and low-risk groups were 44 and 42, respectively. Sixty-three percent of the high-risk and 73% of the low-risk group were premenopausal, Sixty-eight percent of the high-risk and 1 7% of low-risk women had cytologic evidence of hyperplasia with or without atypia ( P < ,0001). Aneuploidy and overexpression of EGFR and p53 occurred in 25%, 36%, and 28% of high-risk subjects but in less than 4% of low-risk subjects ( P < .0002). Overexpression of ER and HER-2lneuoccurred in 8% and 1 respectively of high-risk women; no low-risk women had these abnormalities. Sixty-eight percent of high-risk women and 7% of low-risk women had abnormalities of one or more of these biomarkers exclusive of cytcilogy. Thirty-one percent of high-risk women, but no low-risk women had abnormalities of two or more biomarkers IP = ,0004). Biomarker abnormalities were more frequent with increasing cytologic abnormality. Eighteen percent of women with normal cytology, 29% of women with epithelial hyperplasia and 60% of women with hyperplasia with atypi,] had abnormalities of two or more biomarkers ( P = ,048 and <.0001, respectively). Restricting the analysis to those three biomarkers most frequently overexpressed in the high-risk group (ploidy, ECFR, p53), 13% of high-risk women with normal cytology, 20% of high-risk women with epithelial hyperplasia and 51 YO of high-risk women with atypical hyperplasia had abnormalities of 2 or more of these 3 biomarkers. At a median follow up of two years, 8 of 21 3 women have been diagnosed with in situ (n = 5) or invasive (n = 3) cancer. Later detection of neoplasia was associated with prior FNA evidence of atypical hyperplasia ( P < .0001) and multiple biornarker abnormalities in the 5 test battery ( P = ,006) by univariate analysis. By multivariate analysis, development andlor detection of cancer was primarily predicted by atypical hyperplasia ( P = ,0047) and secondarily by multiple biomarker abnormalities ( P = 0.021). Atypical hyperplasia, EGFR, and p53 in breast FNAs have promise as risk markers and as surrogate endpoint biomarkers for kireast cancer chemoprevention trials.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Identification of a chemoprevention cohort from a population of women at high risk for breast cancer

Fabian¹,

Kamel²,

Zalles³

et al. 1996

J. Cell. Biochem.

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“…The primary endpoint that will be evaluated for response is the change in cytological category between the prestudy and post-treatment aspirations (Table I). In an effort to define a more objective endpoint, changes in a semiquantitative cytological index score [Masood, 1995;Masood et al, 1990] will be studied. We will compare immunocytochemical expression of p53 and EGFR; plus proliferating cell nuclear antigen (PCNA) will be used as an index of proliferation.…”

Section: Current Chemoprevention Trial Using the Fna Modelmentioning

confidence: 99%

Breast cancer chemoprevention trials using the fine-needle aspiration model

Kimler¹,

Fabian²,

Wallace³

2000

J. Cell. Biochem.

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Selection of surrogate endpoint biomarkers (SEBs) and appropriate study design are two of the main challenges in evaluating potential chemopreventive agents. In a prospective random fine-needle aspiration (FNA) study of women at high risk of development of breast cancer, we previously demonstrated that cytologic evidence of epithelial hyperplasia with or without atypia, as well as abnormalities of several cellular biomarkers (DNA ploidy; immunocytochemical expression of p53, EGFR, ER, and/or Her-2/neu), were more prevalent in high-risk women than in low-risk controls. We also demonstrated that the subsequent development of breast cancer was best predicted by an initial presentation of hyperplasia with atypia, as well as by multiple biomarker abnormalities. These findings indicate that FNA cytology and biomarkers can be used to identify women who are appropriate subjects for chemoprevention trials, and can then be used as surrogate endpoint biomarkers to monitor efficacy of potential agents. An example of this use in an ongoing single-agent phase II trial is provided. Several options for study design of possible multi-agent breast cancer chemoprevention trials are discussed, depending upon the existing preclinical and clinical data, the questions being asked, and the number of eligible subjects available. J. Cell. Biochem. Suppl. 34:7-12, 2000. 2000 Key words: biomarker; breast; breast cancer development; chemoprevention; clinical trials; cytology; ER; EGFR; fine-needle aspiration (FNA); Her-2/neu; high risk; p53; ploidy; risk assessment; study design; surrogate endpoint biomarker For phase II trials of potential agents that might prevent breast cancer, one must identify appropriate cohorts of subjects, select optimum tissue biomarkers for testing, standardize tissue sampling methods, and otherwise develop a reliable model for chemoprevention trials [Dhingra, 1995;Dhingra et al., 1993;Fabian and Kimler, 1997;Fabian et al., 1998;Kelloff et al., 1993; O'Shaughnessy, 1996]. The most appropriate subjects for phase II trials will be those who consider themselves at short-term high risk of developing breast cancer and who possess breast tissue biomarkers that are predictive for breast cancer development and are theoretically reversible. BIOMARKERS FROM FINE-NEEDLE BREAST ASPIRATIONSince 1989 at the University of Kansas Medical Center, we have performed breast fineneedle aspiration (FNA) and characterized the aspirated ductal epithelial cells of more than 500 women at high risk of the development of breast cancer on the basis of family history or prior cancerous or precancerous biopsy. The procedures for aspiration, tissue processing, and biomarker analysis have been previously detailed [Fabian et al., 1993[Fabian et al., , 1994[Fabian et al., , 1996[Fabian et al., , 1997cZalles et al., 1995]. Markers studied included cytologic morphology characterization, DNA ploidy, and immunocytochemical expression of p53 [Kamel et al., 1998], epidermal growth factor receptor (EGFR), estrogen receptor (ER), and Her-2/neu.We ha...

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“…Minimally invasive and cost-effective diagnostic sampling procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) have almost replaced open surgical biopsies. Breast-conserving therapy and reconstructive surgery have enhanced cosmetic results, with a positive impact on the sexuality and self-image of patients with breast cancer (1)(2)(3)(4).…”

mentioning

confidence: 99%

“…Furthermore, in the last few years pathologists have gradually evolved from passive interpreters of biopsies and surgical specimens to active clinicians. Pathologists have been engaged not only in interpreting but also in performing minimally invasive procedures such as FNAB, CNB, and ductal lavage (3,27).…”

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confidence: 99%

The Expanding Role of Pathologists in the Diagnosis and Management of Breast Cancer: Worldwide Excellence in Breast Pathology Program

Masood

2003

Breast Journal

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Pathology is the study of human illness and it involves the morphologic and biologic recognition of abnormalities that are associated with a disease. Breast pathology represents an excellent example of this discipline. By providing diagnostic information and by characterizing the biologic behavior of a breast lesion, a pathologist plays a critical role in a patient's life. Any mistake in this exercise is associated with serious consequences. In addition, there are many unresolved issues in breast pathology, which contribute to our limited understanding of the biology of breast cancer, variability in diagnostic criteria, and significant diversity in breast cancer management and therapy. Furthermore, breast pathology has remained an underrecognized discipline, and its importance in diagnosis and disease management is not fully realized. In order to better serve our patients, particularly medically underserved women and those living in countries with limited resources, we must place emphasis on effectively using the talent and expertise of pathologists around the globe. For example, to provide a cost-effective way to diagnose breast cancer, particularly at advanced stages, pathologists can sample lesions by fine-needle aspiration biopsy (FNAB), stain the resulting smears, and provide an immediate bedside diagnosis. This is a valid contribution; however, this exercise requires the availability of a pathologist with experience in breast cytopathology. Alternatively the pathologist may seek consultations from more experienced pathologists. Developing strategies to better recognize the importance of high-quality breast pathology services and to train qualified and innovative breast pathologists is an ambitious task. The proposed Worldwide Excellence in Breast Pathology Program may provide such an opportunity.

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Cytomorphology of Fibrocystic Change, High-Risk, and Premalignant Breast Lesions

Cited by 11 publications

References 30 publications

Identification of a chemoprevention cohort from a population of women at high risk for breast cancer

Identification of a chemoprevention cohort from a population of women at high risk for breast cancer

Breast cancer chemoprevention trials using the fine-needle aspiration model

The Expanding Role of Pathologists in the Diagnosis and Management of Breast Cancer: Worldwide Excellence in Breast Pathology Program

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