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Epithelial Atypia: A Marker Risk of Concomitant or Subsequent Breast Carcinoma?

Department of Pathology, Institut Bergonié, Bordeaux, France

Anne Vincent-Salomon

Department of Pathology, Institut Curie, Paris, France

Simone Mathoulin-Pélissier, Véronique Brouste

Department of Biostatistics, Institut Bergonié, Bordeaux, France

Brigitte Sigal-Zafrani

Department of Tumor Biology, Institut Curie, Paris, France

Marc Debled, Louis Mauriac

Department of Medical Oncology, Institut Bergonié, Bordeaux, France

Christine Tunon de Lara

Department of Surgery, Institut Bergonié, Bordeaux, France

To the Editor:

The study by Degnim et al¹ questions us on breast cancer risk associated with epithelial atypia. In this study, 66 breast cancers (19.9%) occurred among 331 women with ductal and/or lobular atypia (mean follow-up of 13.7 years) from an initial cohort of 9,376 women with benign lesions who underwent surgery between 1967 and 1991. Epithelial atypia were diagnosed on surgical biopsies that had been sampled with a mean of 3.2 slides per specimen. In a recent study, we found a lower absolute risk² associated with epithelial atypia in a series of 2,833 surgical biopsies for microcalcifications without any palpable mass, performed at Bergonié Institute between 1975 and 2003. The surgical biopsies in our series were macroscopically sectioned every 2 mm (median number of slides per biopsy, 26) and ductal and/or lobular atypia were recorded in 971 cases.² A concomitant small ( 5 mm) and low-grade cancer was associated with epithelial atypia in 301 (31%) of 971 of the surgical biopsies. Thus epithelial atypia was isolated, without a concomitant cancer, in 670 of 971 biopsies concerning 415 patients with one or several biopsies and without any previous or synchronous carcinoma in the same or contralateral breast. All these patients were untreated and monitored at our institute (mean follow-up, 13.3 years). Among them, only 18 patients had a subsequent breast cancer (4.3%). Therefore, at 5 and 10 years, the probabilities of developing invasive breast cancer were 2.8% (9 5% CI, 1.4 to 5.5) and 5.5% (95% CI, 3.3 to 9.9), respectively. In light of our experience, we think that the pathologic management of surgical breast biopsies with epithelial atypia is determinant in the estimation of long-term absolute risk of breast cancer. In the study of Degnim et al,¹ as in the other series in the literature,^3-13 estimations of risk associated with epithelial atypia were based on a relatively small number of surgical biopsies with epithelial atypia (n = 60 to 332), extracted from dramatically large series. Surgical biopsies in these series were often performed in the years 1950 to 1970 and were incompletely sampled with (one to six slides per biopsy). During that period, breast surgical biopsies were mainly performed for clinical symptoms (palpable masses, nipple discharge, and so on), and breast imaging techniques were much less accurate than current ones. On the contrary, in our study, extensive macroscopic sampling on surgical biopsies allowed the detection of small concomitant cancers in the vicinity of epithelial atypia. These small cancers might have been missed with a low slide rating, leading to subsequent inadequate patient management. As underlined by Page et al, "the most direct relationship of epithelial atypia incidence is to slide rating."⁴ It is the same for the detection of small carcinomas. Our results strengthen the hypothesis that some ductal epithelial atypia "are a nonobligate, intermediary step in the development of some forms of low-grade in situ and invasive carcinomas."¹⁴ All these in situ and invasive low-grade neoplasia have the same immunophenotype and would belong to the luminal subclass A.¹⁵ In our point of view, pathologic examination is determinant in the estimation of the absolute risk of subsequent cancer associated with epithelial atypia. In conclusion, epithelial atypia could be more a risk marker of concomitant rather than subsequent cancer.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

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2. de Mascarel I, MacGrogan G, Mathoulin-Pélissier S, et al: Epithelial atypia in biopsies performed for microcalcifications: Practical considerations about 2833 serially sectioned surgical biopsies with a long follow-up. Virchows Arch 451:1-10, 2007[Medline]

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10. Shaaban AM, Sloane JP, West CR, et al: Histopathologic types of benign breast lesions and the risk of breast cancer: Case-control study. Am J Surg Pathol 26:421-430, 2002[CrossRef][Medline]

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12. Hartmann LC, Sellers TA, Frost MH, et al: Benign breast disease and the risk of breast cancer. N Engl J Med 353:229-237, 2005[Abstract/Free Full Text]

13. Lewis JT, Hartmann LC, Vierkant RA, et al: An analysis of breast cancer risk in women with single, multiple, and atypical papilloma. Am J Surg Pathol 30:665-672, 2006[CrossRef][Medline]

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15. Abdel-Fatah TM, Powe DG, Hidu Z, et al: Morphologic and molecular evolutionary pathways of low-grade invasive breast cancers and their putative precursor lesions: Further evidence to support the concept of low grade breast neoplasia family. Am J Surg Pathol 32:513-523, 2008[CrossRef][Medline]

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