Continuing Education Activity

Atypical ductal hyperplasia (ADH) is a pathology finding, usually found incidentally on biopsy of the breast. ADH is associated with an increased risk of breast cancer and therefore classified as “high risk” lesion but not precursor lesion - the distinction being the increased risk of breast cancer can be anywhere in the breasts and not limited to the area of the ADH. Depending on the biopsy type - excisional or core - the treatment and management differ. It is important that practitioners be aware of the subtleties in the diagnosis in order to appropriately provide patient care and avoid both under and over-treatment of atypical ductal hyperplasia.

Objectives:

• Describe the pathology findings typical of atypical ductal hyperplasia.
• Explain the impact of the diagnosis on breast cancer risk.
• Outline the surgical risk modification recommendations based on the diagnosis.
• Outline the medical risk modification recommendations based on the diagnosis.

Introduction

Atypical ductal hyperplasia (ADH) is a pathologic finding in breast tissue. Atypical ductal hyperplasia is usually identified incidentally on specimens obtained by needle biopsy prompted by abnormal findings on mammography. Atypical ductal hyperplasia correlates with an increased risk of breast cancer and therefore classified as a "high risk" lesion but is not a "precursor" lesion - the distinction being the breast cancer associated with ADH can occur anywhere in the breasts and not only in the area of the ADH. Because most ADH is found incidentally, the actual incidence is unknown. It is known, once identified, to increase the risk of breast cancer approximately fivefold.[1]

Etiology

The etiology of atypical ductal hyperplasia is unknown; however, ADH is more prevalent in patients with a strong family history of breast cancer.[2] Hoogerbrugge et al. found that nearly 50% of women undergoing prophylactic mastectomies due to high family risk of breast cancer uncovered high-risk lesions, 39% of which were ADH; this suggests that there is a hereditary component involved, which requires further study.

Additionally, a study from 2009 demonstrated that rates of ADH have declined with the loss of favor of post-menopausal hormonal therapies, suggesting this also may have been a contributing factor.[3]

Epidemiology

Atypical ductal hyperplasia, due to its lack of imaging findings, is, by definition, an incidental pathology finding. Most frequently, this is found on core needle biopsy; however, it can also be discovered on excisional biopsies, breast oncologic surgeries, cosmetic breast reductions, or any other breast surgery resulting in submitting breast tissue to pathology. The prevalence of atypical ductal hyperplasia in biopsies has been in the 3.5 to 5% range and most frequently found on core needle biopsy.[4]

Rates of ADH in a large study from 2009 reviewing nearly 31,000 biopsies demonstrated initially increasing rate of diagnosis with the increase in breast cancer awareness, screening mammographies, prophylactic mastectomies, and use of post-menopausal hormonal therapy - resulting in peak diagnosis of ADH in 1999 (5.5 cases per 10,000 mamograms). Since the loss of favor of post-menopausal hormonal therapy, however, there has been a slight decrease in the diagnosis of ADH over time.[3]

Typical patients are females in their fifth to sixth decade of life, as this is the population most likely to be undergoing breast biopsies. Males are also susceptible to atypical ductal hyperplasia, although diagnosis is less common. One Dutch study analyzing over 5,000 cases of excised breast tissue for gynecomastia in males found a prevalence of 0.4% of atypical ductal hyperplasia.[5]

Histopathology

Atypical ductal hyperplasias of the breast are proliferative lesions of the breast that have some, but not all, of the architectural and cytologic features of low-grade ductal carcinoma in situ (DCIS). Specifically, you will find an abnormal accumulation in the ducts of relatively uniform epithelial cells notable for monomorphic round nuclei, regular cell placement, and round regular spaces in at least part of the specimen. What sets it apart from DCIS, however, is that these cells make up only a portion of the specimen.[4][1][6]

History and Physical

Atypical ductal hyperplasia is most often found after biopsy in the setting of calcifications found on mammography or imaging. ADH can also be found incidentally on other breast tissue that is sent to pathology for any number of reasons, including oncologic resections, plastic surgery resections, excisional biopsies, etc. There are no physical findings on the exam, such as a lump, breast discoloration, or breast distortion grossly.

Evaluation

It is important to know the type of specimen in which the ADH is identified because the lesion's management depends on it. 

If atypical ductal hyperplasia is found on core needle biopsy, additional tissue is necessary by excisional biopsy. A wire or seed localization technique should be used at the time of the core biopsy to later identify the area potentially requiring excision. The reason for re-excision is that with a more extensive tissue specimen, there is a chance the lesion will be upgraded to carcinoma in situ or invasive carcinoma. Studies suggest that 22 to 65% of ADH found on core needle biopsies were upgraded to carcinoma after subsequent excisional biopsy.[7][8] Most upgrades are to DCIS; however, IDC is also sometimes found.

If, however, ADH alone is diagnosed on an excisional biopsy, no additional surgery is required, even if there are positive margins because ADH is a high-risk lesion, but it is not a pre-cancerous or cancerous lesion.[1][7][9]

Treatment / Management

Once identifying atypical ductal hyperplasia as the diagnosis and ruling out breast carcinoma, it is essential to address risk reduction strategies.

One such measure is treating these patients with tamoxifen, as the vast majority of lesions are ER+. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen conferred a risk reduction of 86% in women with ADH.[10] Therefore, we recommend the discussion of tamoxifen in patients diagnosed with ADH. Tamoxifen is known to increase the risk of endometrial cancer, stroke, DVT, and PE - particularly in patients over the age of 50. Therefore the risk-benefit discussion starting tamoxifen would need to include consideration of these risks and the decision to begin tamoxifen be patient dependant.

Additionally, it is important to increase surveillance and awareness in the patient.[11][6]

Differential Diagnosis

If a core biopsy identifies atypical ductal hyperplasia, it is important to take a larger excisional biopsy to ensure a large enough specimen to rule out carcinoma of the breast. It is also important to note that on biopsy, low-grade DCIS and ADH share many morphologic similarities. Therefore the pathology specimen at hand should be carefully examined to rule out DCIS.[1]

Surgical Oncology

Atypical ductal hyperplasia has a history of surgical overtreatment. If diagnosed on core needle biopsy, a more extensive excisional biopsy is required to rule out breast carcinoma.[12] If, however, ADH and only ADH is found on excisional biopsy, the patient is surgically complete; this includes cases where margins are positive. As ADH is not cancer, there is no need for node sampling nor any role for mastectomy.

Radiation Oncology

There is no role at this time for radiation therapy in a patient diagnosed only with atypical ductal hyperplasia.

Complications

Complications of atypical ductal hyperplasia result from both over and undertreating the diagnosis. There is a risk of missing a breast carcinoma with undertreatment of ADH and not proceeding with additional tissue sampling.[13][12] There is also a risk of overtreating ADH with aggressive surgeries (e.g., mastectomy or excessively large biopsies) in the setting of no malignancy.[11] There is toxicity risk from chemotherapy agents if ADH is misrecognized as a cancerous or precancerous lesion rather than a high-risk lesion. As discussed above, there are known and well-established complications as a result of tamoxifen that should also merit consideration before starting treatment.

Deterrence and Patient Education

Patients should receive education on the meaning of the diagnosis as well as the actual risk conferred by the diagnosis of atypical ductal hyperplasia. Patients diagnosed with ADH should be followed closely by a clinician, given a higher risk of breast carcinoma in the future.[11] Additionally, standard cancer risk-reducing guidelines are recommended, such as normalizing BMI and smoking cessation.

Enhancing Healthcare Team Outcomes

Atypical ductal hyperplasia is a pathology finding, usually found incidentally on biopsy of the breast. The diagnosis by itself is not a precancerous or cancerous lesion. It is, however, a high-risk lesion, indicating the presence of ADH on pathology flags the patient as one who is fivefold more likely to develop breast carcinoma - in any area of the breasts - in the future. For this reason, the nuance of the cancer risk of the finding of ADH on pathology is more challenging to communicate with the patient.

Regardless of lesion excision, there is still an increased risk to the patient of developing breast carcinoma that will require continued monitoring and screening. The patient may also benefit from tamoxifen therapy as a breast cancer prevention agent, depending on if ER+ and if the patient is suitable for tamoxifen given the side effect profile. (Level I)

It is also crucial that surgeons know the appropriate surgical management of this finding. ADH on core needle biopsy will require needle or seed localized excisional biopsy to rule out nearby breast carcinoma. However, if ADH is found on excisional biopsy to be ADH only - even if margins are positive - the patient is surgically complete. [Level 2]