- Atypical ductal hyperplasia (ADH):
- Is a proliferative epithelial lesion of the terminal ductal lobular unit:
- That typically demonstrates low-grade cytologic atypia and monomorphism combined with epithelial architectural complexity (i.e., cribriforming)
- Is a proliferative epithelial lesion of the terminal ductal lobular unit:
- Histologically:
- ADH and low-grade DCIS are virtually identical:
- The distinction between them is based primarily on the quantity of atypia
present - Currently, the consensus criteria recommend that a diagnosis of DCIS be reserved for:
- Lesions that circumferentially involve two or more membrane-bound spaces (typically ducts) or that measure more than 2 mm in linear extent
- A diagnosis of ADH is rendered for:
- Morphologically identical lesions that fall short of these quantitative criteria
- The distinction between them is based primarily on the quantity of atypia
- ADH and low-grade DCIS are virtually identical:
- Atypical ductal hyperplasia (ADH):
- Is identified in:
- 8% to 17% of all core needle breast biopsy specimens
- Because the distinction between ADH and DCIS relies on the quantity of atypia:
- Sampling is an important concern for ADH
diagnosed on CNB
- Sampling is an important concern for ADH
- Is identified in:
- Multiple studies of upgrade rates for
excision of ADH on CNB, including recent studies with primarily large core biopsy techniques:- Show persistent upgrade rates of 10% to 30%:
- Leading to a recommendation for
excision as the standard of care
- Leading to a recommendation for
- Show persistent upgrade rates of 10% to 30%:
- Surgical excision remains the standard of care after a core biopsy diagnosis of ADH:
- However, given that the majority of ADH cases diagnosed by percutaneous biopsy are not upgraded to cancer:
- Routine excision may represent
overtreatment - Therefore, as has been done for other high-
risk lesions identified on CNB, recent research efforts have attempted to identify factors associated with a low risk of cancer upgrade in order to define a favorable subgroup of
women who may avoid surgical excision with minimal risk of a missed invasive carcinoma
- Routine excision may represent
- However, given that the majority of ADH cases diagnosed by percutaneous biopsy are not upgraded to cancer:
- Several groups have worked to identify features of
women with ADH on CNB who have a very low risk (5%) of upgrade to cancer:- Nguyen et al. previously published criteria by which ADH lesions found on core biopsy could be triaged according to the risk of upgrade to
an associated carcinoma:- In their series of 140 patients, a
number of factors were significantly correlated with the rate of upgrade to carcinoma including:- Removal of less than 95% of calcifications in the absence of an associated mass
- Involvement of two or more terminal duct-lobular units
- The presence of significant cytologic atypia
- The presence of necrosis
- Use of these combined criteria led to:
- An upgrade rate of 3% for the subset of women with low-risk features
- In their series of 140 patients, a
- Ko et al, also developed a scoring system to predict malignancy in patients with a diagnosis of ADH on CNB:
- They found that age older than 50 year, micro-calcification on mammography, size on imaging greater than 15 mm, and a palpable lesion were independent predictors of malignancy
- The presence of focal ADH was a negative predictor
- Similar criteria also have been reported by Pena et al. from the Mayo Clinic:
- In this series of 399 patients, the
overall upgrade rate was:- 16.1%
- The features on core biopsy most strongly associated with upgrade were:
- Percentage of the lesion removed
- Individual cell necrosis
- Number of ADH foci in the core biopsy specimen
- A low-risk subgroup was identified by:
- The absence of individual cell necrosis
- Either one focus of ADH with 50%
removal or more / or more than one focus with 90% removal of the sample
- Using these criteria, approximately one third
of women were identified as low risk for upgrade, and the actual upgrade rate in this group was 4.9%
- In this series of 399 patients, the
- Individual cell necrosis also has been suggested by prior studies showing its association with cancer upgrade
- Pena et al. also evaluated the performance of the Ko et al. and Nguyen et al.85 criteria and found that both models successfully identified women with a low risk of upgrade:
- However the proportion of women assessed to be at low risk was substantially smaller than with the Pena model
- Nguyen et al. previously published criteria by which ADH lesions found on core biopsy could be triaged according to the risk of upgrade to
- The long-term safety of prospectively omitting surgical excision was recently reported by Menen et al. for the low-risk subgroup of women defined by the criteria of Nguyen et al:
- In this series of 175 patients, all meeting
the low-risk criteria, 125 were observed, and 50 underwent excision - During a median follow-up period of 3 years, 14
breast cancer events were noted:- In the surgery group, breast cancer developed in six women (12%), compared with seven cancers (5.6%) in the observed group
- Notably, approximately 75% of the cancer events occurred in the ipsilateral breast, and the majority were outside the index site
- These data suggest that observation rather than surgical excision after a core biopsy diagnosis of ADH may be a safe option for a select subgroup of patients meeting the low-risk radiologic and histologic criteria:
- However, close monitoring and the use of chemoprevention still are indicated because ADH is a marker of increased risk for breast
carcinoma
- However, close monitoring and the use of chemoprevention still are indicated because ADH is a marker of increased risk for breast
- In this series of 175 patients, all meeting
- Caution with omitting surgical excision is further
highlighted by the results reported by Deshaies et al:- In their large retrospective study of 422 ADH cases, the following six factors independently associated with cancer upgrade were identified:
- Severe ADH
- Mammography for ipsilateral symptoms
- Mammographic lesions other than
microcalcifications alone - Co-diagnosis of papilloma
- Use of a 14-gauge needle
- ADH diagnosis performed by
pathologists with low volume
- Of the 422 biopsies, 128 were judged to be low risk because they did not present any
of these six characteristics, yet the upgrade frequency at surgery was substantial (17.2 vs 31.3% for the whole
group):- Thus, these authors were unable to identify a
subgroup of patients for whom excision could confidently be omitted with a low risk of upgrade - Notably, this study did not include the proportion of the lesion removed with
needle biopsy, which appeared to be a key factor in the other aforementioned models that succeeded in identifying a low-risk subgroup
- Thus, these authors were unable to identify a
- In their large retrospective study of 422 ADH cases, the following six factors independently associated with cancer upgrade were identified:
- Despite recent research efforts to identify a low-risks group:
- Surgical excision remains the standard of care after a CNB diagnosis of ADH:
- Particularly in the presence of an associated mass lesion and radiologic-pathologic
discordance
- Particularly in the presence of an associated mass lesion and radiologic-pathologic
- Although promising, the vast majority of
these data have been in retrospective studies, with only one single-institution prospective study investigating a limited number of women:- Therefore, the standard approach remains surgical excision until further prospective studies confirm the validity of these criteria
- For women with ADH diagnosed by CNB, surgical excision is not the only relevant clinical decision in patient management:
- For these women, estimation of their long-
term breast cancer risk is important so they can be advised on surveillance and prevention strategies - Unfortunately, commonly used breast cancer risk models, such as the Gail model and the Tyrer-Cuzick model:
- Do not predict risk very accurately for individual women with atypical hyperplasia
- For these women, estimation of their long-
- For this reason, absolute risk estimation is recommended:
- Based on data from the Mayo Clinic and Nashville Cohorts:
- The risk is approximately 1% per year for women with ADH
- The Partners Cohort has found a somewhat higher risk:
- Approximately 1.7% per year, for women with ADH
- In contrast, recent data from
the Breast Cancer Surveillance Consortium found a lower annual average risk of breast cancer for women with ADH:- Only 0.6% per year, although these data included only invasive breast cancer events and excluded DCIS
- Further work is ongoing to optimize accurate risk assessment for women with ADH
- Based on data from the Mayo Clinic and Nashville Cohorts:
- Surgical excision remains the standard of care after a CNB diagnosis of ADH:
- Another factor shown to stratify long-term risk for women with ADH is the number of ADH foci present within the benign breast biopsy
specimen:- With increasing risk related to increasing foci of
atypia, observed in both the Mayo Clinic and the Nashville Cohorts - This finding was challenged by the Nurses’
Health Study, in which the number of ADH foci did not have a significant impact later on breast cancer risk - Risk estimation is relevant because a lifetime risk greater than 25% would indicate use of magnetic resonance imaging (MRI) for breast cancer screening, whereas risk below that threshold would not
- With increasing risk related to increasing foci of
- Regardless of the means used to estimate long-term breast cancer risk for women with ADH, prevention therapy should be discussed:
- For younger women with an anticipated long life expectancy and a long at-risk period
for breast cancer:- Prevention therapy should be strongly
recommended because their cumulative risk probably exceeds 25%
- Prevention therapy should be strongly
- For older women with competing morbidity,
prevention therapy is unlikely to have any impact on survival and minimal benefit for quality of life because most breast cancers that would develop are likely to be hormonally sensitive:- However, prevention therapy should be
recommended for the majority of women with ADH because their long-term risk is substantial, and prevention medications result in a 70% reduction in breast cancer
risk
- However, prevention therapy should be
- For younger women with an anticipated long life expectancy and a long at-risk period
- Long-term counseling of women with ADH
should include some discussion of long-term breast cancer risk, surveillance strategies, and options for prevention therapy
Rodrigo Arrangoiz MS, MD, FACS, FSSO 