Surgical management of ADH, ALH, and LCIS

The most important implication of finding atypical ductal hyperplasia (ADH) or lobular neoplasia—atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS)—is that the patient is at a significantly increased lifetime risk of developing breast cancer (1–2 percent per year for ADH or ALH, and approximately 2 percent per year for LCIS).^1-3

These patients should be thoroughly informed of breast cancer risk and appropriate surveillance and risk-reduction strategies, which should include consideration of prevention therapy, which has been shown to reduce risk of breast cancer development by as much as 70 percent for women with these high-risk breast lesions.²

For the surgeon, another important issue is when to surgically excise an area of ADH or lobular neoplasia found on core needle biopsy (CNB) to evaluate for potential upstaging to malignancy.

Lobular neoplasia: ALH and LCIS

Lobular neoplasia is a term that includes both ALH and classic LCIS, the distinction being only the percentage of the terminal ductal lobular unit involved (greater for LCIS than ALH). Risk of breast cancer—invasive and ductal carcinoma in situ (DCIS)—is increased for both, approximately a four- to fivefold increased risk for ALH and eight- to ninefold increased risk for LCIS, with both breasts at increased risk. Recent estimates of absolute risk suggest 1–2 percent per year for ALH and 2 percent per year for LCIS.^1-5

Upgrade rates for ALH and classic LCIS on CNB in retrospective studies were wide-ranging in early studies, but more contemporary studies with consistent large core biopsies demonstrate single-digit upgrade rates for pure lobular neoplasia without mass lesion on imaging. Recent studies that distinguish ALH from LCIS show higher upgrade rates for LCIS (7–28 percent) compared with ALH (0–9 percent).^6-8

Thus, the preponderance of evidence indicates that for patients without mass lesions and pure ALH on CNB, routine excision is not required; for patients with pure LCIS (no mass lesion), excision should be considered in the patient’s clinical context. One study has noted higher upgrade rates for lobular neoplasia identified with screening magnetic resonance imaging (MRI), especially in women with prior history of cancer.9 LCIS with comedo-necrosis and pleomorphic LCIS have upgrade rates as high as 40 percent to invasive cancer and should be excised.^10-11

ADH

ADH and low-grade DCIS have an identical histologic phenotype, and the distinction is made primarily on the quantity of atypia present. Because the linear extent of atypia is a criterion for distinction between ADH and DCIS, and because multiple studies have shown an upgrade rate of 10–30 percent for ADH on CNB, surgical excision is the well-established standard of care.¹² Because surgical excision is costly and is a burden on the patient, ongoing research is aimed at identifying a subset of ADH with lower upgrade rates, where excisional biopsy might safely be omitted. Several studies have evaluated factors associated with upgrade in an attempt to identify a subset with low risk of upgrade.^13,14 Common factors identified across these studies include: no mass lesion, removal of a large majority (at least 50 percent) of the lesion seen mammographically, no necrosis, and ADH involving only one or two terminal duct lobular units.

For women with ADH who met these criteria, upgrade rates were only 3–5 percent. However, prospective validation of these criteria is lacking; therefore, surgical excision remains the standard of care for ADH found on CNB.

If safety of omitting surgical excision for the low-risk subgroup of ADH could be established, more than 3,000 women each year might be spared an operation from which they derive no value. As compelling as this goal is, it would be premature to omit surgical excision for ADH on CNB outside of a clinical trial.

Conclusion

Both lobular neoplasia and ADH confer a long-term increased risk of breast cancer, and should trigger discussion of risk-reduction and surveillance strategies. Surgical excision is standard of care for ADH identified on core biopsy, though current research efforts are focused on identifying a subgroup where excision might safely be omitted. Surgical excision is also recommended for “non-classic” LCIS, such as pleomorphic LCIS and LCIS with comedo-necrosis, and for LCIS found on core biopsy of enhancing lesions on MRI. For ALH, growing evidence supports omission of surgical excision when there is no mass lesion, no accompanying ADH, and biopsy was performed by large core vacuum-assisted biopsy with excellent sampling and concordance with the target image. For LCIS, surgical excision should be considered, taking into account the clinical context and patient goals (see Table 1).

Table 1. Excisional biopsy recommendations

References

1. Degnim AC, Dupont WD, Radisky DC, et al. Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women. Cancer. 2016;122(19):2971-2978.
2. Coopey SB, Mazzola E, Buckley JM, et al. The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions. Breast Cancer Res Treat. 2012;136(3):627-633.
3. Menes TS, Kerlikowske K, Lange J, et al. Subsequent breast cancer risk following diagnosis of atypical ductal hyperplasia on needle biopsy. JAMA Oncol. 2017;3(1):36-41.
4. Chuba PJ, Hamre MR, Yap J, et al. Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ: Analysis of surveillance, epidemiology, and end results data. J Clin Oncol. 2005;23(24):5534-5541.
5. King TA, Pilewskie M, Muhsen S, et al. Lobular carcinoma in situ: A 29-year longitudinal experience evaluating clinicopathologic features and breast cancer risk. J Clin Oncol. 2015;33(33):3945-3952.
6. Mooney KL, Bassett LW, Apple SK. Upgrade rates of high-risk breast lesions diagnosed on core needle biopsy: A single institution experience and literature review. Mod Pathol. 2016;29(12):1471-1484.
7. Sen LQ, Berg WA, Hooley RJ, Carter GJ, Desouki MM, Sumkin JH. Core breast biopsies showing lobular carcinoma in situ should be excised and surveillance is reasonable for atypical lobular hyperplasia. AJR Am J Roentgenol. 2016;207(5):1132-1145.
8. Nakhlis F, Gilmore L, Gelman R, et al. Incidence of adjacent synchronous invasive carcinoma and/or ductal carcinoma in-situ in patients with lobular neoplasia: Results from a prospective multi-institutional registry (TBCRC 020). AJR Am J Roentgenol. 2016;23(3):722-728.
9. Khoury T, Kumar PR, Li Z, et al. Lobular neoplasia detected in MRI-guided core biopsy carries a high risk for upgrade: A study of 63 cases from four different institutions. Mod Pathol. 2016;29(1):25-33.
10. Wazir U, Wazir A, Wells C, Mokbel K. Pleomorphic lobular carcinoma in situ: Current evidence and a systematic review. Oncol Lett. 2016;12(6):4863-4868.
11. Flanagan MR, Rendi MH, Calhoun KE, Anderson BO, Javid SH. Pleomorphic lobular carcinoma in situ: Radiologic-pathologic features and clinical management. Ann Surg Oncol. 2015;22(13):4263-4269.
12. Bahl M, Barzilay R, Yedidia AB, Locascio NJ, Yu L, Lehman CD. High-risk breast lesions: A machine learning model to predict pathologic upgrade and reduce unnecessary surgical excision. Radiology. October 17, 2017 [Epub ahead of print].
13. Nguyen CV, Albarracin CT, Whitman GJ, Lopez A, Sneige N. Atypical ductal hyperplasia in directional vacuum-assisted biopsy of breast microcalcifications: Considerations for surgical excision. Ann Surg Oncol. 2011;18(3):752-761.
14. Pena A, Shah SS, Fazzio RT, et al. Multivariate model to identify women at low risk of cancer upgrade after a core needle biopsy diagnosis of atypical ductal hyperplasia. Breast Cancer Res Treat. 2017;164(2):295-304.