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

The Tumour Markers — What They Are and Why They Matter

ER — Oestrogen Receptor

PR — Progesterone Receptor

HER2 — Human Epidermal Growth Factor Receptor 2

Ki-67 — Proliferation Index

CA 15-3 — Cancer Antigen 15-3

CEA — Carcinoembryonic Antigen

Why Complete Documentation Matters

Why Serum Over-Ordering Is a Problem

1. The result is meaningless — a normal result does not rule out cancer (the patient already has cancer), and a raised result does not change management in early disease.
2. It wastes resources — laboratory time, reagent costs, and reporting time are spent on a test that will not alter the patient's treatment pathway.
3. It causes patient anxiety — a mildly elevated CA 15-3 (which can happen in benign conditions) may prompt unnecessary further investigations, scans, and patient worry.

Why Turnaround Time Delays Matter

• IHC (immunohistochemistry — the staining test for ER/PR/Ki-67) and FISH (the confirmatory gene test for HER2 when IHC is equivocal) are processed in different labs
• Samples are batched and only run twice a week
• Reporting backlogs exist

Now — What the Analysis Terms Mean in Simple Language

Compliance Rate per Standard

Turnaround Time (TAT) Analysis

• Mean TAT — the average number of days across all patients
• Range — the fastest and slowest case (e.g. 2 days to 14 days)
• % meeting the ≤5 day target — what proportion of patients had their results within the recommended window

Serum Marker Appropriateness

• Appropriate — patient has known metastatic disease and the test is being used to monitor treatment response ✅
• Inappropriate — patient has early-stage breast cancer and the test was ordered at initial diagnosis ❌
• Unclear — the reason for requesting is not documented in the notes ⚠️

Gap Analysis

Pulling It All Together — Why Are We Doing This?

• Breast cancer treatment is now highly personalised — the same drug does not work for every patient
• The biomarkers described above are the tool that personalises it
• If those biomarkers are missing, delayed, or the wrong tests are being ordered, patients may receive the wrong treatment, wait longer than necessary, or have unnecessary worry caused by irrelevant test results
• Guidelines from the world's top cancer organisations (ASCO, ESMO) set clear rules for what should happen — this audit checks whether local practice matches those rules

Week 1 — Setup & Governance

Day 1 (Today) — Talk to Your Supervisor

• Approach your named consultant supervisor (ideally in oncology or breast surgery)
• Say something like: "I'd like to run a clinical audit on breast tumour marker documentation as my QI project. I've drafted a proposal — would you be willing to supervise it?"
• Show them the QI project outline from our previous conversation (you can print or email it)
• Ask them specifically:
  • Can they be named supervisor / co-author?
  • Who is the right person in the pathology/lab department to contact?
  • Is there a breast MDT coordinator you should speak to?
  • Does the hospital use paper notes or electronic records (EPR)? Which system — ICE, EMIS, Meditech, Sunrise, other?

Day 2 — Register the Audit

• Ask your supervisor or ward secretary where the clinical audit department is, or find it on the hospital intranet
• Go in person or email them and say: "I am a final-year medical student undertaking a clinical audit on breast tumour marker documentation. I would like to register this project. Can you send me the registration form?"
• Fill in the registration form. It will typically ask for:
  • Project title
  • Your name and supervisor's name
  • Department and specialty
  • Aim of the audit
  • What data you will collect
  • Where you will store data (answer: anonymised spreadsheet on a trust computer or trust-approved secure drive — never personal laptop or personal email)
  • Approximate number of cases (put 30–50)
  • Whether patients will be contacted (answer: No — case note review only)

Day 3 — Build Your Data Collection Spreadsheet

Day 4 — Understand the Data Sources

• Ask your supervisor or a registrar to show you where the following live in your hospital's system:
  • Pathology reports — this is where ER/PR/HER2/Ki-67 results will be (look for "histopathology report" or "immunohistochemistry report" in the EPR or ICE system)
  • MDT records — the breast MDT meeting outcomes, usually recorded in the EPR or a dedicated MDT database (iMDT, MDT Manager, or a Word document in some hospitals)
  • Laboratory request records — where you can see what blood tests (CA 15-3, CEA) were ordered and by whom
  • Clinic letters — the oncologist's letter after the first appointment, which should summarise the biomarker results
• Ask: "Can I be given supervised read-only access to the EPR to review case notes for the audit?" Your supervisor or the audit department will facilitate this.

Day 5 — Identify Your Patient List

• Ask your supervisor or the MDT coordinator for a list of all newly diagnosed breast cancer patients discussed at the breast MDT over the last 6–12 months
• Alternatively, ask the pathology department for a list of all breast cancer histopathology reports issued in that period
• You do not need names — a list of hospital numbers is enough (the audit department will advise on how to handle identifiable data)
• Aim for consecutive cases (the last 30–50 patients in chronological order) — this avoids selection bias

End of Week 1 — Checklist

• Supervisor identified and agreed
• Audit registered with the clinical audit department
• Project reference number obtained
• Data collection spreadsheet built and saved securely
• Data sources identified (pathology system, MDT records, lab requests)
• EPR read-only access confirmed or in progress
• Patient list obtained or formally requested
• Attended (or arranged to attend) a breast MDT meeting

Common Week 1 Mistakes to Avoid

• Do not start collecting patient data before the audit is registered. Even looking at notes with intent to record data counts as data collection.
• Do not save anything with patient names or NHS numbers — use your own patient ID numbers from the start.
• Do not email patient data to a personal Gmail/Hotmail account. Use only trust systems.
• Do not try to do this alone — your supervisor is there to open doors. Use them.

What Week 2 Looks Like (Preview)

1. Do you need to tell the department about the standards before you start?

• Register the project with the audit department (this is an administrative step, not a clinical announcement)
• Tell your supervisor privately — they need to know, and they may already be aware of gaps
• Keep it quiet from the wider clinical team until data collection is complete
• After analysis, you present the findings formally — that is when you share the gaps and recommendations

2. Are you trying to improve practice right now, or just observe?

Measure what is currently happening and compare it against the guideline standard.

• Share the data with the department
• Recommend changes (e.g. a standard pathology request form, a checklist for the MDT)
• Re-audit in 6–12 months to see if compliance has improved (this is called a completed audit cycle and is what makes a project publishable)

3. Retrospective (past patients) or prospective (new patients from now)?

Retrospective (recommended for you)

• You look back at patients already diagnosed and treated — typically the last 30–50 consecutive breast cancer cases from the MDT records
• Advantages: Data already exists. You can collect 30–50 cases in 1–2 weeks. The audit is complete before your placement ends. No waiting.
• Disadvantage: The data is historical, so you cannot change anything that happened to those patients — but that is fine, because you are measuring the system, not individual patients.

Prospective (not recommended for your situation)

• You recruit newly diagnosed patients from this week forward and follow their journey in real time
• Advantages: You can observe the process as it happens and capture more detail
• Disadvantages: Breast cancer diagnoses come through slowly — you might only see 5–10 new patients in an 8-week attachment, which is not enough for a meaningful audit. You would also need to wait weeks for all results to come in before you can analyse anything. You would likely run out of placement time before you have enough data.

4. Do you need to consult the breast pathology team to make sure all markers are being tested?

• Asking for read-only access to pathology reports (administrative request, facilitated by your supervisor)
• Recording what is and is not in the reports

• Telling pathologists they should be including Ki-67 in every report
• Requesting additional staining on past specimens
• Inserting yourself into the clinical workflow

Summary — The Four Answers in One Place

One Final Point — What This Makes Your Project