Abstract P4-12-07: Single pre-operative radiation therapy (SPORT) trial for low risk breast cancer: A phase 1 study comparing pathological findings in immediate versus delayed surgery

Abstract Introduction: Estrogen receptor (ER)-positive/HER2-negative breast cancers are known to be less immunogenic than triple negative and HER2-positive breast cancers. As increasing levels of tumor-infiltrating lymphocytes (TILs) have been associated with increased rates of pathological complete response (pCR) and improved prognosis, there is interest in exploring ways to render ER-positive/HER2-negative breast cancers more immunogenic. Few studies have analysed the histological response to neoadjuvant radiation therapy (RT) as the only pre-operative treatment modality; in most case series, chemotherapy was concomitantly given, as these studies focused on the treatment of advanced breast cancer. Aims: The objectives of this study are to assess pathological and immunological responses induced by a single dose of pre-operative RT in early breast cancer. Material and methods: women aged 60 years or older diagnosed with invasive breast carcinoma were prospectively identified. Only cT1N0 unifocal tumors that were low to intermediate grade and ER-positive/HER2 negative were eligible. Patients received a single pre-operative radiation dose of 20Gy in a single fraction. Surgery was performed either 24-72 hours after RT (SPORT group) or 11-13 weeks after RT (SPORT -DS [delayed surgery] group). Assessment of pathological response was performed using the Miller-Payne system and Residual Cancer Burden was calculated. Immunohistochemistry for Ki67 was performed on the biopsy and excision specimens. CD8 immunostain was used to evaluate the immune infiltrate. Both groups (SPORT and SPORT-DS) were compared using the independent t-test and Fisher exact test. Results: a total of thirteen patients were included, with an average age of 73 years (range 60-84). All patients received a single 20Gy radiation dose, and surgery was performed either 24-72 hours after RT (SPORT group, n=5) or on average 95 days after RT in the SPORT-DS group (range 75-133 days; n=8). All patients underwent partial mastectomy with sentinel lymph node biopsy. Histologically, all tumors were invasive ductal carcinomas, except for one invasive micropapillary carcinoma and one invasive tubular carcinoma (both in the SPORT group). Tumor bed changes, similar to what is observed in the post-neoadjuvant chemotherapy setting, were identified in all but one patients in the SPORT-DS group (7/8 patients) but was not seen in the SPORT group (0/5 patients, p=0.005). Using the Miller-Payne system, there was no evidence of response in the SPORT cohort (grade 1/5 in all patients), while 6/8 patients in the SPORT-DS cohort had a partial pathological response (grade 3/5 in 2 patients and grade 4/5 in 4 patients, p = 0.02). No pCR were observed. Comparing Ki67 on the biopsy and surgical specimens, an average decrease of 7.5% in the SPORT group and 6.3% in the SPORT-DS group was observed (p=0.8). A significant lymphocytic infiltrate was not present in any case (stromal TILs <10% in all cases). At an average follow-up of 11 months, there have been no recurrences. Conclusion: This is, to our knowledge, the first series comparing histological findings from immediate and delayed surgery after pre-operative single dose RT. We observed a significant decrease in tumor cellularity with delayed surgery, while no change in cellularity occurred with immediate surgery. The lack of lymphocytic infiltrate does not support immune activation as the mechanism of the ablative effect of 20Gy of radiation. Further follow-up will be needed to determine the prognostic significance of the partial pathological response that was observed in the SPORT-DS cohort. Citation Format: Marie-Hélène Ngo, David Tiberi, Peter Vavassis, David Nguyen, Bernard Fortin, Mai-Kim Gervais, Lucas Sideris, Pierre Dubé, Guy Leblanc, Michel-Pierre Dufresne, Marie-Christine Guilbert, Michael Yassa. Single pre-operative radiation therapy (SPORT) trial for low risk breast cancer: A phase 1 study comparing pathological findings in immediate versus delayed surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-07.

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