Breast cancer biomarker discordance between primary and sites of metastasis: A systematic review.
Bibliographic record
Abstract
e11574 Background: Systemic treatment choices for breast cancer patients with recurrent disease are usually based on the ER/PR/Her2 biomarker status of the primary cancer. Biomarker discordance between the primary and metastatic sites is well recognised and could have important therapeutic implications. A systematic review was conducted to assess the extent of biomarker discordance between the primary cancer and metastasis, and whether is influenced by the site of metastasis. Methods: An electronic search of multiple literature databases implemented by an information scientist was conducted to identify studies reporting outcomes of ER/PR/Her2 receptor stability between primary site and recurrent disease. Seven reviewers independently screened the 5034 abstracts and full text articles, which were identified according to pre-defined selection criteria. The same reviewers performed data collection from all included studies. Studies that were identified reported on receptor conversion between primary sites of breast cancer and various sites of metastasis including lymph node, liver, brain, lung, skin, GI sites and bone marrow. Results: Preliminary results from 385 eligible studies consistently demonstrated discordance between the primary and metastatic sites. When discordance occurred, the general trend was for loss of hormone receptor. ER hormone status was more stable (discordance 10.2-32.5%) than PR (discordance 25.5-40.7%). HER2 was found to have lower rates of discordance (2.6-14.5%). In general, higher ER/PR discordance was found in bone (40-68%) and liver (0-54%) when compared to other sites brain (36%), lung (9-18%), skin (6-22%), GI (15-40%). In the prospective studies, biomarker discordance led to change in patient management in up to 20% of the patient population. Conclusions: Our results demonstrate that biomarker discordance between primary and distant metastases does occur in breast cancer, occurs more frequently with PR, and the extent of discordance is influenced by the site of metastasis. Further research is required to have a better explanation about the pathophysiology of the biomarker status change and its clinical implications.
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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 | 0.020 | 0.079 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.008 |
| Bibliometrics | 0.013 | 0.015 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".