Breast Lesion Cancer Risk Depends on Where the Atypia Sits, Study Finds

When a breast biopsy reveals a radial sclerosing lesion — a benign growth whose tangled, star-shaped architecture can mimic cancer on a mammogram — surgical guidelines currently treat one accompanying finding as a red flag demanding immediate removal: epithelial atypia. A new observational cohort study from The University of Texas MD Anderson Cancer Center, published in Breast Cancer Research and Treatment, suggests that this one-size-fits-all recommendation may be too blunt. By tracking 105 such lesions diagnosed on image-guided needle biopsy between July 2020 and May 2025, the researchers found that the risk of finding malignancy at the lesion site varied dramatically depending on two factors that prior studies had rarely separated: the specific type of atypical cells present, and whether those cells sat inside the radial sclerosing lesion itself or merely in the neighboring breast tissue sampled by the same needle.

The headline number comes from the highest-risk subgroup. Among the 24 lesions in which atypical ductal hyperplasia, or ADH, involved the radial sclerosing lesion itself, the estimated cumulative incidence of ductal carcinoma in situ (DCIS) or invasive cancer at the lesion site reached 29.2 percent at three years, with a 95 percent confidence interval stretching from 15.1 to 51.6 percent. Surgical excision was performed for 22 of those 24 lesions — 91.7 percent — and seven of the excised specimens were upgraded to malignancy, six of them DCIS and one invasive cancer. In other words, when ADH was woven into the architecture of the radial lesion, roughly one excision in three uncovered a cancer, a figure that strongly supports the existing guideline to remove such lesions.

The picture changed sharply when the atypia was located elsewhere. For the 35 lesions in which ADH was found only in the tissue adjacent to the radial sclerosing lesion, the three-year cumulative incidence of malignancy was 8.6 percent (95 percent CI: 2.8 to 24.3 percent). Excision rates in this group were far lower — 17 of 35 lesions, or 48.6 percent — reflecting the institution’s multidisciplinary approach, and only three of the excised lesions were upgraded, two with DCIS and one with invasive cancer. Lowest of all was the group with lobular neoplasia or other atypia — including atypical lobular hyperplasia, classic lobular carcinoma in situ, flat epithelial atypia, and atypical apocrine proliferations — whose three-year cumulative incidence was just 2.2 percent (95 percent CI: 0.3 to 14.4 percent), whether or not the atypia involved the lesion itself. The difference across subgroups was statistically significant, with a log-rank test p-value of 0.001.

Notably, not a single malignancy emerged during follow-up. All eleven cancers in the study were identified at surgical excision performed shortly after the initial biopsy diagnosis. Among the lesions left under imaging surveillance, three later underwent excision because their radiologic appearance changed — one with adjacent ADH and two with lobular neoplasia or other atypia — and none of these harbored DCIS or invasive cancer. With a median clinical and radiologic follow-up of 2.8 years (interquartile range: 1.7 to 4.1 years), the cumulative incidence estimates remained stable through five years of observation. The authors caution, however, that malignancy or its radiologic progression could still emerge over longer timeframes, and that continued surveillance of unexcised lesions is essential.

To place these findings in context, the team first conducted a systematic review of the existing literature, searching Ovid MEDLINE, Ovid Embase, and the Cochrane Library in October 2025 for studies published after 2004 that included at least five radial sclerosing lesions with associated atypia diagnosed by image-guided core biopsy and reported oncologic outcomes. Of 334 studies identified, 20 met the inclusion criteria. The reported probability of malignancy at surgical excision varied enormously across those studies, from zero percent to at least 60 percent, and only four studies stratified upgrade rates by atypia subtype. In the two largest of those, lesions with ADH carried a higher probability of malignancy than those with lobular neoplasia — 35 percent versus 12 percent in one, and 24 percent versus 6 percent in the other. Just one prior study had separated atypia involving the lesion from atypia in adjacent tissue, and both malignancies it reported arose in lesions where the atypia involved the radial sclerosing lesion itself.

The methodological novelty of the new study lies in that anatomic distinction. Pathology reports were independently reviewed by breast pathologists to verify each diagnosis, and atypia was classified as involving the radial sclerosing lesion if it was described as involving, arising from, or within the ducts and lobules emanating from the lesion; atypia seen in the non-lesional tissue also sampled during the core biopsy was classified as adjacent. The cohort was drawn from MD Anderson’s electronic health records and excluded patients with concurrent invasive cancer, DCIS, or pleomorphic lobular carcinoma in situ in the same breast, as well as those with other atypia at distant sites, to isolate the risk attributable to the biopsy-diagnosed lesion itself.

The 105 lesions belonged to 104 patients with a median age of 59 years at diagnosis. A family history of breast cancer was reported in 73 cases (69.5 percent), and six patients (5.7 percent) carried a known breast-cancer-associated pathogenic variant. The targeted imaging abnormality was architectural distortion in the plurality of cases — 39 lesions, or 37.1 percent — with calcifications and masses making up the remainder. Strikingly, concurrent invasive cancer in the opposite breast was present in 22 cases (21.0 percent), distributed in similar proportions across the atypia subgroups, underscoring that many of these patients were already under intensive oncologic evaluation when the radial lesion was discovered.

Management at the institution reflected a deliberately nuanced protocol. Surgical excision was routinely recommended when epithelial atypia involved the radial sclerosing lesion. For lesions with only adjacent atypia, the recommendation — excision or observation — was made case by case through a weekly multidisciplinary conference of radiologists, pathologists, surgeons, and high-risk cancer prevention practitioners, who weighed factors such as the proportion of the targeted lesion sampled, the biopsy modality, radiologic-pathologic concordance, the number of terminal duct lobular units involved, and the presence of necrosis. For lobular neoplasia identified incidentally, active monitoring was typically recommended. This selective practice is what generated the subgroup variation the study was designed to measure, though the authors acknowledge it also means excision decisions were not randomized.

The statistical approach aimed to estimate outcomes under continuous surveillance. Observations were censored at the date of expected annual imaging if a patient exceeded a yearly interval without breast imaging, and cumulative incidences were calculated with the Kaplan-Meier estimator using complementary log-log confidence intervals. Because all outcome events occurred shortly after initial diagnosis, the estimated cumulative incidence was stable through five years. The authors are candid about the limitations: subgroup sample sizes were small, producing wide confidence intervals; not all lesions were excised, and lesions without atypia involving the lesion were less likely to be excised, so estimates in the lower-risk groups could rise with longer follow-up; and the median imaging follow-up of 2.8 years may be too short to capture malignancies that develop or progress slowly.

Even with those caveats, the study offers the most granular risk stratification yet for a lesion type that has long been managed by a single rule. The authors conclude that excision remains well supported when ADH involves a radial sclerosing lesion, but that for other atypia types — and for ADH confined to adjacent tissue — the decision can be adapted to the individual clinical context, incorporating the type and extent of atypia, imaging-pathologic concordance, patient preferences, and the feasibility of reliable surveillance. They emphasize that any observation strategy should emerge from shared decision-making with patients counselled on risk-reducing therapies and committed to annual imaging, ideally after multidisciplinary review has excluded radiologic-pathologic discordance or inadequate sampling. Implementing active surveillance on the basis of this evidence, they warn, should be done with caution — but for selected patients, the scalpel may no longer be the only reasonable answer.

Subject of Research: Cancer upgrade risk after biopsy diagnosis of radial sclerosing breast lesions with epithelial atypia

Article Title: Risk of malignancy after diagnosis of radial sclerosing lesion with associated atypia

Article References: Delgado Casanova, L. B., Dhamne, S., Resetkova, E., Guirguis, M. S., Geng, Y., Bevers, T. B., Bedrosian, I., Huo, L., & Wanis, K. N. (2026). Risk of malignancy after diagnosis of radial sclerosing lesion with associated atypia. Breast Cancer Research and Treatment, 220(1), Article 18. https://doi.org/10.1007/s10549-026-08103-3

Image Credits: AI Generated

DOI: 10.1007/s10549-026-08103-3

Keywords: radial sclerosing lesion, atypical ductal hyperplasia, breast biopsy, surgical excision, lobular neoplasia, DCIS, imaging surveillance, breast cancer risk, core needle biopsy, epithelial atypia, observational cohort study, MD Anderson