Percutaneous image-guided biopsy has greatly reduced the need for open excisional biopsy in obtaining a diagnosis for a mammographic abnormality. ADH is present in a significant proportion of benign core biopsy specimens. Following a diagnosis of ADH, it is currently recommended that excisional biopsy follow to rule out underlying malignancy. The reasons for this include significant inter- and intraobserver variation among pathologists when diagnosing ADH, histologic similarities between ADH and DCIS, and the potential for under sampling of the lesion due to a relatively small sample size obtained by percutaneous biopsy.
In this study of patients with mammographic abnormality followed by stereotactic biopsy, we demonstrated an upgrade rate of 14.9% at our institution, which is at the lower end of the historically quoted range, though still too high to recommend observation to all patients with ADH on stereotactic biopsy. We further attempted to identify low-risk features that when present could reassure a low likelihood of upstaging of ADH to DCIS or invasive breast cancer. We found in our population that age, personal or family history of breast cancer, breast density, and the number of cores removed were not associated with risk of upgrade. Though none of these features reached statistical significance, there was a trend toward low risk for an upgrade if ADH was not associated with the target calcifications (incidental) or if ADH was focal (limited to 1-2 foci). Features that were significantly identified as low risk for upgrade included lesions smaller than 1cm, >50% of the lesion removed by stereotactic biopsy, and if ADH was associated with micropapillary features.
The literature has been varied as to what patient demographic, radiologic, and pathologic findings have been associated with a higher risk of an upgrade at the time of surgical excision, emphasizing the importance of understanding one’s patient population and radiologic and pathologic resources. Jensen et al. were one of the first to describe micropapillary features and extent of ADH to be associated with a higher rate of upgrade, both of which we were found to be significantly associated with upgrade in our study. Similar to other studies, we found the percent of the lesion removed and the size of the lesion to also be a risk of upgrade upon excision.[9,13,16,17] Patient demographic features such as age at diagnosis of ADH and family history of breast cancer as risk factors[18,20] were not reproducible in our study.
There have been no randomized controlled trials to determine the need for surgical excision of ADH. Interestingly, we continue to push the edge of where we are comfortable de-escalating surgical intervention. There are currently several trials actively enrolling, one in the US (AFT-25 COMET, NCT02926911) and two in Europe (LORD NCT02492607 in the Netherlands and Belgium, LORIS in the UK), attempting to identify which patients with DCIS can be offered active monitoring over excision. Separating ADH from low-risk DCIS can be controversial and arbitrary, fraught with interobserver variability and lacking biological validation. Some accept Tavassoli’s definition of DCIS being >2mm, regardless of the number of involved ducts and others prefer Page’s original proposal that DCIS must include at least two fully involved duct cross-sections. In our patient population, when ADH upgraded to malignancy, the majority (n=10, 77%) met criteria for low-risk DCIS, acceptable for randomization in the above mentioned trials (grade I-II and hormone-receptor positive). Though not yet standard of care, if COMET concludes a low rate of progression to IBC when surgical excision is omitted for low risk DCIS, and this becomes accepted as standard of care, only 3 of the 87 biopsies with ADH (3.4%) would have benefited from surgical excision and identification of a more aggressive underlying malignancy.
Our study has several limitations, including the retrospective nature of this analysis and the relatively small sample size. Also, there is potential for selection bias in that all of our patients had to undergo surgical excision to be included in the analysis. There were multiple patients during this time period that were excluded because it was determined they did not need surgical excision or the patient declined excision. One patient who did upgrade did not have biopsy slides or imaging available for re-review, which may have limited the strength of our findings. However, the strengths of this study included the contemporary time frame of our study, the re-interpretation of all available patients’ imaging and biopsy slides by breast-specific radiologists and pathologists for the above detailed characteristics, and the extensive length of follow-up.
In summary, we were able to conclude that for patients with ADH identified on stereotactic biopsy, the overall risk of upgrade to underlying malignancy is lower than historically quoted, though may still be too high to offer active monitoring to all. With careful radiologic and pathologic correlation, patients with the lowest risk for upgrade to DCIS or IBC may be selected, allowing clinicians to appropriately offer alternatives to surgical excision. Our study was able to demonstrate that the lowest risk for upgrade in our patient population are those with an imaging target of <1 cm in size, >50% of the lesion removed by the percutaneous biopsy, 1-2 foci of ADH, and the absence of micropapillary features. Further application of these low-risk criteria in a prospective manner will be necessary, including the management of ADH identified by other imaging modalities. The oncologic safety of surgical de-escalation and offering active surveillance for ADH will also be necessary to establish in future studies.