Pilewskie Highlights Trends for Surgical Management of High-risk Breast Lesions

High-risk, or B3, breast lesions present in a variety of ways and have varying associated risks of developing or upgrading into a malignancy. B3 lesions have historically been managed with surgery via excision; however, new monitoring techniques have shown the potential to replace surgery in certain situations.

In an interview with OncologyLive^®, Melissa L. Pilewskie, MD, director of the Breast Care Center and a faculty member in the Department of Surgery at Michigan Medicine in Ann Arbor, highlighted some of the primary components of her presentation concerning high-risk breast lesions, which will be delivered during the 40th Annual Miami Breast Cancer Conference^®.

“My presentation will review data assessing utility of surgical excision for different high-risk lesions, including atypical hyperplasia, lobular carcinoma in situ [LCIS], papilloma of the breast, and flat epithelial atypia,” Pilewskie said. “In addition, I will review available data on outcomes for cohorts of patients who have undergone observation alone with these lesions. Lastly, strategies for assessing long-term risk associated with select high-risk lesions and limitations in risk calculators for these specific populations will be reviewed.”

Atypical ductal hyperplasia (ADH) is diagnosed in up to 17% of percutaneous biopsies and can upgrade to ductal carcinoma in situ or invasive carcinoma from core needle biopsy to excision in as much as 62% of patients. Additionally, patients with ADH are at 4 to 5 times higher risk for invasive breast cancer compared with the normal population.¹

In a systemic review and meta-analysis of 6458 ADHs, Schiaffino et al examined 5911 cases that were managed with surgical excision and 547 cases managed with follow-up alone. Study authors found that the pooled upgrade rate was 29% (95% CI, 26%-32%) for lesions that were surgically excised compared with 5% (95% CI, 4%-8%) for ADHs treated with follow-up (P < .001). Investigators noted that there was high heterogeneity in their findings and that, due to a pooled upgrade rate exceeding 2%, ADH diagnosed with a percutaneous needle biopsy should be managed with surgical excision.²

LICS has an upgrade rate to malignancy of approximately 22% and patients with LCIS have a 4 to 12 times higher risk of developing breast cancer vs women without lobular neoplasia. For lobular neoplasia overall, the upgrade rate following surgical excision can climb as high as 40%, although it varies widely across different studies.¹

Papillomas of the breast are rare, appearing in approximately 3% of all breast cancers, and are most common in women aged 30 years to 50 years. Papillary lesions can include solitary intraductal papillomas, multiple intraductal papillomas, and papillomas with atypia, among other classifications. Upgrade rates for papillomas have a wide range, with some being as low as 3.1% and others climbing above 70%.¹

According to the U.K.’s National Health Service Breast Screening program, papillomas with atypia should be managed with surgical excision.³ For other types, there are multiple management options.

Flat epithelial atypia is observed in approximately 2% of benign breast biopsies and is often discovered secondary to microcalcifications, or in association with other high-risk breast lesions. The upgrade rate to malignancy flat epithelial atypia is approximately 11%.¹

Wahab et al performed a systemic review and meta-analysis and concluded that pure flat epithelial atypia should be surgically excised due to a high pooled upgrade rate. In their analysis of 2482 cases of pure flat epithelial atypia, the pooled upgrade rates were 5% (95% CI, 3%-6%), 1% (95% CI, 0%-2%), and 2% (95% CI, 1%-3%) for breast cancer, invasive carcinoma, and ductal carcinoma in situ, respectively. Notably, the pooled upgrade rate to breast cancer was 0% when more than 90% of calcifications were removed at core needle biopsy.⁴

However, consensus on how to manage many of these high-risk lesions has not yet been reached. According to the Second International Consensus Conference on B3 lesions, excluding ADH, many B3 lesions can be managed with more frequent vacuum-assisted biopsy as opposed to the traditional first-line open surgical excision.⁵

What would you say is the most significant recent advance in high-risk breast lesions, and why? How does this advance apply to clinical practice/fill an unmet need in the space?

The most significant advance in this area is the individualization of whether a high-risk lesion requires surgical excision. Previously, the presence of any one of these diagnoses on a core needle biopsy would result in the recommendation for surgery. With the available data, we are now able to better assess the likelihood of upgrade to carcinoma and therefore the potential benefit of surgical excision based on clinicopathologic features. This practice shift will result in a substantial decrease in the need for surgical excision for benign breast disease.

What are some needs in this space that remain unmet? Is there any planned research to address them?

There is an additional pending prospective study assessing upgrade rates for flat epithelial atypia, which is anticipated soon. Furthermore, there is a need to identify uniform, evidence-based criteria for selective observation for a subset of patients with atypical ductal hyperplasia.

[Additionally], there is interest in providing personalized risk assessment for individuals with several breast cancer risk factors, including high-risk lesions. While risk calculators provide relatively accurate assessments for women with a family history of breast cancer, studies show lower accuracy among cohorts of patients with atypical hyperplasia and LCIS, details that are now incorporated into current NCCN [National Comprehensive Cancer Network] guidelines. Given these limitations with the Gail model and Tyrer-Cuzick model, there is a need to identify tools to provide more accurate risk assessment for these moderate risk cohorts.

What are some exciting future developments in the high-risk space?

In addition to high-risk lesion management, other exciting developments related to the high-risk population pertain to novel approaches to risk reduction, including topical chemoprevention and exercise, [which are] topics of ongoing research.

What is the big-picture takeaway from your presentation for clinicians?

[The] implementation of current surgical recommendations for high-risk lesions are important to avoid overtreatment of certain benign breast lesions. While the surgical management is shifting, it remains paramount to counsel women with atypical hyperplasia and lobular carcinoma in situ on long-term risk and options for risk reduction.

References

1. Catanzariti F, Avendano D, Cicero G, et al. High-risk lesions of the breast: concurrent diagnostic tools and management recommendations. Insights Imaging. 2021;12(1):63. doi:10.1186/s13244-021-01005-6
2. Schiaffino S, Calabrese M, Melani EF, et al. Upgrade rate of percutaneously diagnosed pure atypical ductal hyperplasia: systematic review and meta-analysis of 6458 lesions. Radiology. 2020;294(1):76-86. doi:10.1148/radiol.2019190748
3. Pinder SE, Shaaban A, Deb R, et al. NHS Breast Screening multidisciplinary working group guidelines for the diagnosis and management of breast lesions of uncertain malignant potential on core biopsy (B3 lesions). Clin Radiol. 2018;73(8):682-692. doi:10.1016/j.crad.2018.04.004
4. Wahab RA, Lee SJ, Mulligan ME, Zhang B, Mahoney MC. Upgrade rate of pure flat epithelial atypia diagnosed at core needle biopsy: a systematic review and meta-analysis. Radiol Imaging Cancer. 2021;3(1):e200116. doi:10.1148/rycan.2021200116
5. Rageth CJ, O’Flynn EAM, Pinker K, et al. Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions). Breast Cancer Res Treat. 2019;174(2):279-296. doi:10.1007/s10549-018-05071-1