High-Risk and Premalignant Lesions of the Breast

Introduction

Some breast lesions have been termed “high risk” for either (1) an immediate risk of breast cancer due to underdiagnosis by percutaneous biopsy or (2) a long-term increased risk of future breast cancer (hence the term “premalignant”). The classical lesions in this group are atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS). For decades, these lesions have been recognized to portend a higher long-term risk of breast cancer, but precise predictions of long-term risk remain elusive. In spite of the “premalignant” moniker, definite pathways governing progression to cancer are yet to be elucidated. The majority of women with these findings do not develop future breast cancer, leading to the hypothesis that these lesions are nonobligate precursors of breast cancer. In the early era of percutaneous diagnostic biopsies, surgical excision of these lesions was recommended because of upstaging to a finding of cancer in a minority of cases. Recent research on women with these lesions has refined recommendations about when surgical excision is suggested, how to estimate their long-term risk and risk-reduction strategies that should be considered. This chapter will review both the immediate risk of upgrade to cancer and the long-term risk of breast cancer for atypical hyperplasia (AH) and LCIS.

Classic High-Risk Lesions

ADH, ALH, and LCIS are considered the “classic” high-risk breast lesions, as they were identified many years ago as being associated with an increased future risk of breast cancer. In 1941 Foote and Stewart first described LCIS, and in the 1970s its association with breast cancer was reported as approximately 1% per year and equal across both breasts. In 1985 Dupont and Page reported an approximate fourfold increased risk of breast cancer in women with ADH or ALH compared with the general population. With the shift to percutaneous core needle biopsy for diagnosis, current relevant management questions focus on which lesions require surgical excision to rule out underlying cancer, and how these patients should be managed regarding increased long-term cancer risk.

Surgical Excision of High-Risk Lesions

In the 1990s percutaneous core needle biopsy was introduced for the diagnosis of breast abnormalities. The main benefit of percutaneous biopsy is the ability to obtain a diagnosis without a surgical procedure; conversely, its primary limitation is the possibility of sampling error, as the procedure obtains a sample of the lesion that is usually incomplete. Furthermore, the lesion is fragmented into multiple smaller pieces, which can increase the difficulty of making a definitive histologic diagnosis.

Because of sampling error, cancer could potentially be missed with percutaneous core needle biopsy, and certain histologic diagnoses carry a substantial risk of finding cancer (i.e., “upgrade”) when the biopsy site is surgically excised. Many studies have evaluated factors associated with the likelihood of upgrading to cancer and, as would be expected, factors most consistently identified are those that relate to the thoroughness of sampling, including the size of the lesion, the percentage of the lesion removed percutaneously, and the size and type of biopsy device (i.e., 14G needle vs. 9–11G vacuum-assisted biopsy devices).

For these reasons, it is important to correlate the mammographic findings with the percutaneous biopsy pathologic findings and to understand which lesions should be surgically excised. The goal of surgical excision is to remove the biopsy site and the original imaging lesion to obtain a definitive diagnosis regarding the possible presence of cancer.

Percutaneous Biopsy Concordance Assessment

Radiologic-pathologic concordance is the current standard of care in practices that perform percutaneous needle biopsy (whether the biopsy is guided by palpation, or by ultrasound, or stereotactic imaging). Concordance assessment includes a combined assessment of clinical, imaging, and pathologic findings that are judged to be internally consistent. Radiologists, pathologists, and surgeons are typical key members involved in concordance assessment.

The surgeon’s role in assessing concordance includes a review of the abnormality in the original diagnostic mammograms, as well as in the post-biopsy imaging, to assess how much of the lesion remains after percutaneous biopsy and whether the biopsy marker is located at the site of the original lesion. The pathology findings are then interpreted in the context of the clinical and imaging findings to determine if they are all in clinical agreement. If there is concern that the imaging lesion was not sampled, or if the pathology is discordant with the imaging lesion, surgical excision should be performed for definitive diagnosis.

Description of ADH, ALH, and LCIS

ADH was defined in 1985 as an epithelial proliferative lesion of the terminal duct lobular unit with both cytologic atypia and architectural changes, qualitatively similar to ductal carcinoma in situ (DCIS) but lesser in quantity. The size and extent of ADH are smaller, involving only one or two ducts and measuring less than 2 mm, so it does not meet the criteria for DCIS. Therefore tissue fragments from percutaneous needle biopsy of a DCIS lesion could appear to be ADH.

ALH and LCIS constitute two types of lesions along the spectrum of lobular neoplasia. LCIS was first described by Foote and Stewart in 1941 and is defined microscopically by filling and distention of at least half of the acini of a lobular unit with confluent growth of small, bland-appearing monomorphic cells with small nuclei. ALH is similar histologically to LCIS but is less extensive, involving less than half of the acini of a lobule. Despite the similar morphology of the cells to those seen with LCIS, ALH lacks the accompanying marked expansion of the acini.