---

Quality Improvement Programme Proposal

Optimising Breast Tumour Marker Investigation in the Oncology Department

---

1. Background and Rationale

• Over-ordering of serum tumour markers (CA 15-3, CEA) for screening or early detection, where evidence is insufficient
• Under-ordering of tissue biomarkers (ER/PR/HER2/Ki-67) on all newly diagnosed carcinomas
• Lack of repeat testing at metastatic recurrence, where receptor discordance is documented in 10–30% of cases
• Poor harmonisation of CA 15-3 and CEA assays across platforms, causing inter-laboratory variation of up to 29% — identified as a major patient safety issue in a 2025 external quality assessment study (Van Rossum et al., Clin Chem Lab Med 2025, PMID 39299928)
• Delayed turnaround times for actionable biomarkers, impacting time-to-treatment

---

2. Aim Statement

"Within 12 months, to achieve ≥95% compliance with evidence-based guidelines for breast tumour marker ordering, reporting, and utilisation across the oncology department, reducing inappropriate test requests by ≥30% and improving turnaround time for actionable tissue biomarkers to ≤5 working days in ≥90% of cases."

---

3. Objectives

1. Appropriateness: Ensure all newly diagnosed breast carcinomas receive ER, PR, HER2, and Ki-67 tissue assessment at initial diagnosis.
2. Re-testing at recurrence: Ensure biopsy with repeat biomarker panel is performed at metastatic relapse in ≥90% of eligible patients.
3. Serum marker rationalisation: Reduce inappropriate ordering of CA 15-3/CEA for screening or primary diagnosis (not guideline-indicated).
4. Turnaround time (TAT): Achieve TAT for tissue biomarkers (IHC/FISH) ≤5 working days in ≥90% of cases.
5. Molecular testing: Ensure eligible patients (HR+/HER2-, metastatic/high-risk) undergo BRCA1/2, PIK3CA, and ESR1 mutation testing per ASCO 2024 and ESMO 2024 guidelines.
6. Assay harmonisation: Implement internal QC protocols for CA 15-3 and CEA in line with EQA harmonisation standards.
7. Patient communication: Ensure patients receive timely, documented communication of biomarker results and their therapeutic implications.

---

4. Standards and Guideline References

---

5. Methodology — PDSA Cycle

Phase 1: PLAN (Months 1–2)

• Retrospective review of 100 consecutive breast cancer cases over the preceding 12 months
• Data collection on:
  • Proportion with complete tissue biomarker panel (ER/PR/HER2/Ki-67) at diagnosis
  • Proportion undergoing biopsy/re-testing at metastatic relapse
  • Frequency of serum CA 15-3 / CEA requests by indication category (screening vs. monitoring vs. inappropriate)
  • TAT for IHC and FISH reports
  • Rates of BRCA1/2 and molecular testing in eligible patients
  • Assay platform used for CA 15-3 and CEA (for harmonisation audit)

• Oncologists, histopathologists, clinical biochemists, breast surgeons, clinical nurse specialists, laboratory scientists

• Why are markers not ordered? (knowledge gap, system gap, capacity)
• Why are markers over-ordered? (habit, patient pressure, lack of protocol)
• Why are TATs delayed? (laboratory capacity, prioritisation)

---

Phase 2: DO (Months 3–8)

---

Phase 3: STUDY (Month 9)

---

Phase 4: ACT (Months 10–12)

• Sustain effective interventions; embed in departmental SOP
• Address residual gaps with second PDSA micro-cycle
• Escalate persistent TAT issues to laboratory management
• Share results at departmental governance meeting and submit abstract to BASO or ASCO annual meeting
• Incorporate findings into the annual NAPBC / national accreditation submission (required every 3 years from Jan 2026 per ACS Cancer Programs)

---

6. Key Performance Indicators (KPIs)

---

7. Governance and Accountability

---

8. Risk Register

---

9. Expected Outcomes and Benefits

• Patient safety: Reduced risk of missing actionable targets (ER, HER2, PIK3CA, ESR1) that could direct life-changing therapies
• Clinical quality: Alignment with ASCO 2024, ESMO 2024, and ASCO-CAP 2023 — Gold Standard accreditation evidence
• Resource efficiency: Elimination of inappropriate serum marker requests reduces laboratory costs
• Equity: Standardised pathways ensure all patients receive equivalent, protocol-driven biomarker workup regardless of treating clinician
• Education: Workforce upskilling in evolving biomarker landscape (HER2-low, ESR1, PIK3CA, ctDNA liquid biopsy)
• Research enabler: Complete, harmonised biomarker datasets support future translational and clinical research

---

10. References & Evidence Base

1. Loibl S et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159–182.
2. Henry NL et al. Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update. J Clin Oncol. 2022. (Updated rapid recommendations 2023–2024)
3. Van Rossum HH et al. External quality assessment-based tumor marker harmonisation simulation: insights in achievable harmonisation for CA 15-3 and CEA. Clin Chem Lab Med. 2025. [PMID 39299928]
4. Garrido-Castro AC et al. Biomarkers in breast cancer 2024: updated consensus statement, SEOM-SEAP. PMC11564209.
5. ASCO-CAP HER2 Testing Guidelines. 2023 update.
6. ACS/NAPBC QI Standard 7.3 — mandatory QI project per accreditation cycle, effective January 2026.
7. Henry's Clinical Diagnosis and Management by Laboratory Methods, 23rd ed. — Chapter 76 (Tumour Markers); Chapter 75 (HER2/neu Receptor).
8. Tietz Textbook of Laboratory Medicine, 7th ed. — Use of Tumour Markers in Specific Malignancies.

---

Where it's appropriate for a medical student:

• The concept and topic are excellent. Choosing breast tumour markers as a QI focus shows clinical relevance, awareness of guidelines, and genuine oncology interest. Examiners and supervisors will find this impressive.
• The problem statement, rationale, and background are well within a medical student's scope to write.
• Identifying the gaps (over-ordering serum markers, incomplete tissue panels, TAT delays) is exactly the kind of critical thinking expected.
• The PDSA cycle framework is standard for medical student QI projects and is appropriate here.

Where it's too advanced for a student-led project:

Recommendation for a medical student version:

"An audit of whether all newly diagnosed breast cancer patients in the oncology clinic have a documented ER, PR, HER2, and Ki-67 result recorded in their notes at the time of treatment planning discussion."

---

Quality Improvement Project

Adherence to Evidence-Based Breast Tumour Marker Testing at Initial Diagnosis: A Clinical Audit in an Oncology Outpatient Setting

---

1. Background

• Eligibility for endocrine therapy (ER/PR positive)
• Eligibility for anti-HER2 therapy (trastuzumab, pertuzumab, T-DXd)
• Chemotherapy intensity (Ki-67 proliferation index)
• Prognostic subtype (Luminal A/B, HER2-enriched, Triple Negative)

---

2. Aim

"To audit whether patients with newly diagnosed breast cancer discussed at the oncology MDT or seen in clinic have a complete, documented tissue biomarker panel (ER, PR, HER2, Ki-67) available at the time of initial treatment planning, and to identify whether serum tumour markers (CA 15-3, CEA) are being ordered appropriately."

---

3. Standards (Audit Criteria)

---

4. Method

Data Collection

• Sample size: 30–50 consecutive newly diagnosed breast cancer patients discussed at MDT or seen in oncology clinic during your attachment
• Data source: Electronic patient records / MDT records / pathology system
• Design: Retrospective case note review (no patient contact needed — this usually avoids formal ethics approval and falls under local clinical audit registration)

Data Points to Record (per patient, anonymised)

• Age, tumour stage (I–IV)
• Date of pathological diagnosis
• Date of MDT/first oncology clinic
• ER documented: Yes / No / Date
• PR documented: Yes / No / Date
• HER2 IHC documented: Yes / No / Date
• HER2 FISH performed (if IHC 2+): Yes / No / N/A
• Ki-67 documented: Yes / No / Date
• Serum CA 15-3 ordered: Yes / No → if yes, documented indication: Monitoring / Screening / Primary diagnosis / Unclear
• Serum CEA ordered: Yes / No → if yes, documented indication
• Interval from biopsy to full biomarker panel available (days)
• Treatment decision documented: Yes / No

Tool

---

5. Analysis

• Descriptive statistics: Percentage compliance for each standard, presented as bar charts
• Turnaround time: Mean and range of days from biopsy to complete biomarker result
• Appropriateness of serum markers: Frequency table of indication categories
• Gap analysis: Which standard shows the lowest compliance? Which patient subgroup is most affected?

---

6. Expected Findings (Based on Literature)

• ER/PR/HER2 documentation is generally high in well-organised centres but Ki-67 and FISH reflex rates are more variable
• Serum CA 15-3 over-ordering for non-metastatic patients is a recognised problem in several audits
• Turnaround time gaps are common when IHC and FISH are processed by different laboratories

---

7. Recommendations (to Generate from Your Findings)

1. Implement a standardised pathology request form that automatically includes ER/PR/HER2/Ki-67 as a bundle for all breast core biopsies
2. Introduce a MDT checklist item — "Complete biomarker panel available? Y/N" — before treatment decisions are recorded
3. Develop a departmental guideline for serum marker ordering with clear indication criteria
4. Feed findings into the oncology governance/audit meeting as a change recommendation

---

8. Pathway to Publication or Presentation

---

9. Ethical Considerations

• Register the project with the local clinical audit department (not formal ethics — case note review is audit, not research in most jurisdictions)
• All data must be anonymised (use a patient ID number, never name or NHS/hospital number in your spreadsheet)
• Store data on a trust-approved, password-protected system — not personal devices or personal email
• Confirm data access permission with your clinical supervisor before starting

---

10. Why This Project Works for a Final-Year Student

---

Quick Summary — What You Need to Do

1. Week 1: Register with local audit department; get supervisor sign-off; build your data collection spreadsheet
2. Weeks 2–7: Collect anonymised data from 30–50 case notes
3. Week 8: Analyse, produce bar charts, calculate compliance rates
4. Week 9–10: Write up findings + recommendations; present at local audit meeting
5. Month 3: Submit abstract or manuscript to a suitable journal/conference