Quality-of-Life Measurement in Patients With Metastatic Breast Cancer

As the first and only dedicated quality-of-life module for metastatic breast cancer, the EOTC QLQ-MBR44 was shaped by 187 patients and 41 clinicians, and it signals how patient-reported evidence may be collected next.

Image

Why Did Existing Quality-of-Life Tools Fall Short for Metastatic Breast Cancer?

Many innovative cancer drugs meet their first patients in the metastatic setting. Those patients then may complete questionnaires built mainly for early-stage disease.

A tool that cannot detect change in advanced cancer may miss both the benefits and the burdens of a new therapy. Closing that gap meant asking patients and clinicians directly, then testing every answer against the published evidence.

The measurement gap

Metastatic breast cancer (MBC) is treatable but still incurable.

Breast cancer accounts for almost 12% of all cancers worldwide. Between 13% and 23% of patients with early disease develop metastatic recurrence, and 3% to 12% present with metastases at diagnosis in developed countries. In developing countries, de novo MBC can reach 60%.

Yet no MBC-specific patient-reported outcome measure exists. The EORTC QLQ-C30 is used most often, followed by FACT-B and the QLQ-C30 paired with the QLQ-BR23.

Existing breast cancer modules were built mainly in early-stage disease. They may miss changes that matter in MBC, where patients were rarely involved in early questionnaire design. That matters to drug developers, because many innovative therapies are first tested in MBC. A generic tool can overlook patient-centred adverse effects or benefits.

The ABC Global Alliance has named quality of life and psychosocial support as priority gaps for this metastatic cancer population. The new EOTRC module has been built to do exactly that..

Phase 1: content generation

The tool’s development team followed the EORTC module development guidelines. They anchored the work in the UK Department of Health’s Generic Choice Model for long-term conditions. It covers six themes, from symptom burden to support pathways.

A systematic review of literature from 2000 to 2019 screened 11,416 papers and included 103.

Of these, 70 were phase III trials of medicinal products and 33 were observational or qualitative studies. A parallel review of investigator brochures covered 29 treatments: 12 chemotherapies, nine targeted therapies, seven endocrine therapies, and one immunotherapy.

Together, the reviews produced 185 candidate issues. Between July 2020 and March 2021, the team interviewed 41 healthcare professionals and 187 women with MBC across eight countries. Patients ranged from in age 29 to 85 years old, with a median age of 59.

Each participant rated every issue for relevance and chose the 15 most important.

Patient data took priority. The team set four prespecified thresholds on relevance and importance, and included issues that met three or more. This narrowed 185 issues to 44.

Phase 2: item development

The team searched the EORTC Item Library, which holds more than 1,070 items. Novel wording was needed where no suitable item existed. Expert review then removed five overlapping issues and restored “sore mouth”, given its clinical significance with newer treatments.

The provisional module holds 40 issues assessed by 44 items. Of these, 34 come from the library, seven are modified, and three are new. Sexual issues sit at the end so patients can skip them, because some cultures may find such questions inappropriate.

The proposed scales are:

• Physical symptoms and side effects: 10 items
• Fear and uncertainty: Nine items
• Family impact: Five items
• Musculoskeletal pain: four items
• Sexual issues: Four items
• Treatment and disease impact: Three items
• Independence: Three items

• Fatigue, body image, and anxiety-depression: Two items each

  Image

  

What Patients and Clinicians Rated as Most Important

Clinicians and patients do not see the disease in the same way.

Clinicians rated almost every issue as relevant, with 44% (81 of 185) averaging above 3.0. Patients rated fewer than half as relevant, with 39% (73 of 185) averaging above 2.0.

The patient list leaned towards issues that are psychological. Eight of the top 10 patient issues were psychological.

Only fatigue and lack of energy were physical. Fear of disease progression and worry about family led the ranking.

Five of the top 10 issues overlapped between the two groups, mostly around worries and fears. Fatigue was the most relevant physical issue for both. Among physical symptoms, hair loss drew the highest priority share from patients, at 28.6%.

Age shaped the final quality-of-life issues list. Four issues were borderline for the full sample but stayed in because they mattered to younger patients. They were needing help from family or children, parenting worries, vaginal dryness, and body image dissatisfaction.

The team also tested the core QLQ-C30 against MBC. Clinicians rated all 28 items highly relevant.

Patients rated 16 of 28 as relevant, favouring role function, family and social impact, emotional function, pain, fatigue, concentration, and sleep. They scored nausea, appetite loss, constipation, diarrhoea, breathlessness, and financial difficulties lower.

The developers conclude that the new module should sit alongside the QLQ-C30, not replace it. A stand-alone approach could miss important issues.

View interview Is AI Quietly Creating a GDPR Crisis in Clinical Research?

Is AI Quietly Creating a GDPR Crisis in Clinical Research?

Generative AI is transforming clinical trials, but a failure to distinguish between pseudonymised and anonymised data is creating costly regulatory gaps.

Image

Why is QoL in MBC QoL Important for Clinical Trials?

There has been no agency review of the module. Its relevance for industry lies in how trials will capture patient experience.

Consider the wider debate on evidence.

A 2025 commentary in The Breast examined the FDA and EMA approvals of datopotamab deruxtecan, granted without survival data. The author called for critical examination of those evidence standards.

In general, when survival evidence is incomplete, credible patient-reported data on how people feel carries more weight. Pharmatica’s Insights into the endpoint lessons for gynaecological cancer trials demonstrates this well.

The new MBC EORTC module also fits existing work. The Health Outcomes Observatory consortium built a core outcome set for MBC with 101 variables. The new questionnaire has comparable issues, apart from six items, including cough, headaches, and rash.

The overlap supports the content coverage of the QLQ-C30 plus the new module.

What sponsors should for focus on for QoL in MBC: 

• The tool now is provisional. Phase 3 testing is underway. Phase 4 field testing must still confirm acceptability, reliability, validity, responsiveness, and cross-cultural use.
• Psychosocial items need careful handling. Such issues may not suit all trials of new treatments. They plan a summary score of mainly physical symptoms, similar to the FACIT trial outcome index.
• Newer drugs may be under-covered. The literature review used dates from 2019. Agents such as trastuzumab deruxtecan, tucatinib, and abemaciclib were assessed through investigator’s brochure review only.
• Scope is female patients. A separate EORTC module for male breast cancer is in development.
• Commercial use carries fees. EORTC states that commercial use of its instruments involves licence fees, while academic use is free.

Readers should also note the funding. The EORTC Quality of Life Group supported the work, and two authors disclosed relationships with pharmaceutical companies.

Sponsors comparing instruments, such as those in the EuroQoL framework, should weigh this context.

Patient Voice Moves From to the Endpoint

The EORTC QLQ-MBR44 is the first quality-of-life module built specifically for MBC. It rests on 103 papers, a review of 29 treatments, and 228 interviews. It distills 185 issues into 40, assessed by 44 items.

It remains provisional and must be used with the QLQ-C30.

Still, it shows that quality of life can now be measured on its own terms for patients with metastatic breast cancer. The next question is whether trial sponsors will adopt it once validation is complete.

At Pharmatica, we track how evidence standards, trial design, and patient-reported data are shaping Clinical Development. Our Insights help pharma leaders judge which methodological shifts deserve action now and which still need proof.

Pharmatica: Insight. Connection. Impact.