Abstract Introduction Accelerated partial breast irradiation (APBI) for invasive lobular carcinoma (ILC) is conditionally not recommended in the 2024 ASTRO Clinical Practice Guidelines. This recommendation stems from the limited number of women with ILC, as opposed to ductal carcinoma, included in landmark APBI trials, and lack of subtype-specific data. This study evaluates APBI in patients with low-risk ILC. Methods and Materials This single-center retrospective study included early-stage breast cancer patients who underwent lumpectomy for ILC or carcinoma with a lobular component. Patients comprised two groups: those who received APBI and those who received whole breast irradiation (WBI). Log-Rank tests were used to compare WBI vs. ABPI for ipsilateral breast tumor recurrence (IBTR), disease-free survival (DFS) and overall survival (OS), while Fisher’s exact tests were used to compare WBI vs. ABPI for toxicities (CTCAE v5.0) and physician-reported cosmesis (Harvard Scale). Results Among patients treated from January 2015 to March 2025, 200 patients met inclusion criteria, 36 (APBI) and 164 (WBI). The median age was 66 years (IQR: 58-71). Pure ILC was present in 179 patients (89.5%), while 21 (10.5%) had mixed lobular and ductal components. Most patients had pT1 tumors (77.5%), grade 1-2 (96.5%), negative margins (98%), estrogen receptor-positive tumors (98%), received endocrine therapy (91.5%), and had no lymphovascular invasion (98.5%). All patients were clinically node-negative, and the median Oncotype score was 18. APBI patients were older (median 69 vs. 64 years; p 0.01) and more likely to have T1 tumors (91.7% vs. 74.4%; p = 0.03). Baseline characteristics, such as tumor grade and receptor status, were similar between groups. 3D conformal RT was used exclusively in both groups. Most patients (92.5%) were treated in the prone position. APBI regimens included 28.5 Gy in 5 fractions on non-consecutive days (61.1%) and 38.5 Gy in 10 twice-daily (BID) fractionation (38.9%). WBI regimens included 40 Gy in 15 fractions (33.5%) and 42.56 Gy in 16 fractions (53.7%). 74.5% of WBI plans used a tumor bed boost. The median follow-up was 4.7 years. The 5-year IBTR was 2.8% in the APBI group and 0.6% in the WBI group (p = 0.26). The 5-year DFS was 97.2% (APBI) and 97.5% (WBI), p = 0.50, and the 5-year OS was 100.0% in APBI group and 97.6% in WBI group (p = 0.45). No Grade 3 or higher acute toxicities occurred. Common Grade 1-2 acute toxicities were fatigue (63.9%) and dermatitis (77.0%). Dermatitis was significantly more common in WBI group (86.6%) than in APBI group (34.3%; p 0.01). Grade 2 dermatitis was observed in 15.4% with WBI vs. 0% with APBI. Among those patients with Grade 1-2 late toxicities at 1 year, common findings in both groups included skin induration (70.9%), hyperpigmentation (55.7%), and breast atrophy (53.5%). One WBI patient experienced Grade 3 breast atrophy. Skin hyperpigmentation was more common in WBI group than in the APBI group (61.8% vs 35.0%, p-value=0.04). One- and 3-year physician-reported cosmesis were similar. Data were available for 138 patients at 1 year. Excellent or good cosmetic outcomes were reported in 93.1% (APBI) and 93.6% (WBI), p = 0.67. At 3-years, cosmetic outcomes were available for 74 patients. Excellent or good cosmesis was 90% (APBI) and 89.1% (WBI), p-value = 0.20. Conclusions In our experience, APBI appears to be a safe and effective treatment option for select patients with low-risk ILC who undergo endocrine therapy. In addition, cosmesis appears equivalent at 1- and 3-years follow up. However, given the potential for late recurrences in hormone receptor-positive disease, longer follow-up is necessary. We plan to continue this investigation with additional patient data on IBTR and survival rates, as well as long-term toxicity and cosmesis. Citation Format: T. Jitwatcharakomol, R. Young, D. L. Handley, S. Beyer, T. Andraos, J. Eckstein, D. Agnese, S. Obeng-Gyasi, R. Wesolowski, K. Johnson, S. Jhawar. External beam accelerated partial breast irradiation versus whole breast irradiation for invasive lobular carcinoma: a retrospective, single-institution study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-07-24.
Jitwatcharakomol et al. (Tue,) studied this question.