Abstract P5-13-17: PD-L1 expression in breast to brain metastases
Bibliographic record
Abstract
Abstract Background Brain metastases (BrM) are a major cause of morbidity and mortality in women with breast cancer. Immunotherapy has the potential for intracranial efficacy among patients with breast cancer since intracranial response to immunotherapy has been observed among patients with other solid tumors. The aim of the study is to analyze the immunohistochemical expression of programmed death ligand 1 (PD-L1), a predictive biomarker of response to immunotherapy, in breast cancer BrMs. Methods A retrospective cohort study of consecutive patients who underwent surgery for breast cancer BrM at Sunnybrook Health Sciences Centre between July 1999 and June 2013 were identified through the Anatomic Pathology departmental database. A tissue microarray using 1um cores was obtained. Immunohistochemical expression of PD-L1 in BrM tissue was assessed in triplicate; PD-L1 positive status was defined as PD-L1 expression ≥1% in tumor infiltrating cells as a percentage of tumor area using the Ventana SP142 antibody. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status was determined using 2018 ASCO/CAP guidelines. Results The median patient age at the time of BrM diagnosis was 52 (range 32-85). ER, PR and HER2 status was available in 58 of 59 cases as follows: 12 (20.3%) triple negative (TNBC), 14 (23.7%) HER2+/HR-, 14 (23.7%) HER2+/HR+, 18 (30.5%) hormone receptor (HR)+/HER2-. The majority 62.7% (n=37) of patients had a solitary BrM. The median size of BrM was 2.9 cm (range 0.3 cm to 6.2 cm) with the most common location being the cerebellum and frontal lobe. The majority of patients (n=51, 86.4%) had symptomatic BrM. The most common sites of extra-cranial metastases were bone (37%), lung (32%), liver (22%), lymph nodes (18.6%), and chest wall (3.4%). After surgical excision of BrM, 88.1% of patients received adjuvant stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT). 39% of patients received at least 1 line of systemic therapy for metastatic disease prior to the development of BrM. The median follow-up for BrM events was 16.1 months. PD-L1 status was available for all 59 patients. In the overall cohort, 9 out 59 (15.3%) breast cancer BrM were PD-L1 positive irrespective of subtype. The frequency of PD-L1 positive BrM by subtype is as follows: TNBC (n= 3/12, 25%), HER2+/HR- (n=3/14, 21.4%), HER2+/HR+ (n=1/14, 7.1%), and HR+/HER2- (n=2/18, 11.1%). Expression of PD-L1 in BrMs was not associated with patient age at the time of BrM diagnosis, size or location of the BrM, grade of the BrM nor breast cancer subtype. At 24 months, brain-specific progression-free survival (bsPFS) was 47.5% (95% CI 32.9-68.7%). When stratified by PD-L1 status, 24-month bs-PFS was 66.7% (95% CI 37.9-100%) among patients with PD-L1 positive BrM versus 42% (95% CI 26.6-67.3%) among those with PD-L1 negative BrM (log-rank p-value 0.142). Conclusion One in 7 patients in our cohort had PD-L1 positive BrM; this proportion was highest (25%) among those with TNBC. Hence, there is rationale to include patients with breast cancer BrM in clinical trials evaluating efficacy of immunotherapy. Citation Format: Rania Chehade, Maleeha A Qazi, Marguerite Ennis, Sharon Nofech-Mozes, Katarzyna Jerzak. PD-L1 expression in breast to brain metastases [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-17.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".