# Patient-Reported Quality of Life 6 Years After Breast Cancer

Maria Alice Franzoi, Antonio Di Meglio, Stefan Michiels, Emma Gillanders, Catherine Gaudin, Anne Laure Martin, Ines Vaz-Luis

► To cite this version:

Maria Alice Franzoi, Antonio Di Meglio, Stefan Michiels, Emma Gillanders, Catherine Gaudin, et al. Patient-Reported Quality of Life 6 Years After Breast Cancer. JAMA Network Open, 2024, 7 (2), pp.e240688. 10.1001/jamanetworkopen.2024.0688. inserm-04639753

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**Research Letter** | Oncology

# Patient-Reported Quality of Life 6 Years After Breast Cancer

Maria Alice Franzoi, MD; Antonio Di Meglio, PhD; Stefan Michiels, PhD; Emma Gillanders, BSc; Catherine Gaudin, BSc; Anne Laure Martin, PhD; Ines Vaz-Luis, MD, PhD

## Introduction

Cancer contributes greatly to the global burden of chronic illness and has a tremendous impact on patient's quality of life (QOL), including physical, emotional, and social domains.¹ The impact that cancer and its treatment have on an individual's health trajectory can vary substantially, meaning that some patients require more care resources than others.²

Previous work³ focused on a group of patients with early stage I to III breast cancer (BC) treated with adjuvant chemotherapy identified a cluster of patients with poor initial QOL and subsequent severe, persistent postchemotherapy QOL deterioration up to 4 years after diagnosis. The current study aims to expand our previous work to unselected patients with BC to identify latent clusters of patients at risk for QOL deterioration up to 6 years after diagnosis and to assess the association of actionable host factors and health behaviors with QOL membership trajectory.

## Methods

This cohort study followed the STROBE reporting guidelines. We performed a longitudinal analysis of QOL using a large, national, prospective cohort in France (Chronic Toxicities Related to Treatment in Patients With Localized Cancer [CANTO])⁴ of patients with stage I to III BC treated from 2012 to 2018. This study was approved by French regulatory authorities and the French Committee for the Protection of Patients, and written informed consent was obtained from patients before participation.⁴

QOL (EORTC Quality of Life Questionnaire C30 summary score³) was assessed at diagnosis (baseline) and 1, 2, 4, and 6 years after diagnoses. Baseline clinical, sociodemographic, behavioral, tumor-related, and treatment-related characteristics were available. Trajectories of QOL and group membership associations were identified by iterative estimations of group-based trajectory models and multivariable multinomial logistic regression, respectively. Data were analyzed May 5, 2023, using SAS statistical software version 9.4 (SAS Institute), including the PROC TRAJ package, and R statistical software version 4.0.3 (R Project for Statistical Computing) with the MICE package. A 2-sided *P* < .05 was considered statistically significant.

## Results

Among 10 792 patients (mean [SD] age, 56.3 [11.2] years; 7982 [78.0%] with a partner; 5725 [57.3%] with monthly household income of <€3000; as of February 1, 2024, €1 = $1.09 US), 5695 received adjuvant chemotherapy and 8805 received adjuvant endocrine therapy. In the overall cohort, 4 QOL trajectory groups were identified: excellent (4934 participants [45.8%]), very good (3596 participants [33.3%]), deteriorating (1745 participants [16.1%]), and poor (517 participants [4.8%]) (Figure, panel A). Patients in the deteriorating trajectory group reported good baseline QOL (score, 73.3; 95% CI, 72.4-74.2), which significantly worsened at year 1 (score, 63.0; 95% CI,

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Open Access. This is an open access article distributed under the terms of the CC-BY License.
62.1-63.9) and never recovered to pretreatment values through year 6 (score, 64.7; 95% CI, 63.3-66.0).

Common factors associated with membership in the deteriorating group in the overall cohort included younger age (adjusted odds ratio [aOR] for 10-year decrement, 1.10; 95% CI, 1.05-1.16), overweight (aOR vs lean, 1.90; 95% CI, 1.60-2.25), obesity (aOR vs lean, 1.25; 95% CI, 1.07-1.46), physical inactivity (aOR vs active, 1.13; 95% CI, 1.04-1.35), smoking behavior (aOR current vs never, 1.16; 95% CI, 0.98-1.36; former vs never, 2.14; 95% CI, 1.80-2.54), Charlson Comorbidity Index score 1 or greater (aOR vs 0, 1.56; 95% CI, 1.33-1.83), lower monthly household income (aOR for <€3000 vs ≥€3000, 1.50; 95% CI, 1.30-1.72), receipt of adjuvant chemotherapy (aOR vs no, 1.35; 95% CI, 1.14-1.59), and receipt of adjuvant endocrine therapy (aOR vs no, 1.46; 95% CI, 1.22-1.75) **(Table)**. Independent analyses of factors associated

<figure><img src="image_4.png" /><figcaption>Figure. Trajectories of Quality of Life After Breast Cancer</figcaption></figure>

Graphs show EORTC Quality of Life Questionnaire (QLQ-C30) scores for all 10 792 patients (A), 5076 patients not treated with adjuvant chemotherapy (B), and 5695 patients treated with adjuvant chemotherapy (C). Dashed lines denote 95% CIs.
<table><caption>Table. Variables Associated With Quality of Life Trajectories in the Overall Cohort</caption><thead><tr><th rowspan="2">Variable</th><th colspan="2">Very good (n = 2865 [33.9%])</th><th colspan="2">Deteriorating (n = 1312 [15.5%])</th><th colspan="2">Poor (n = 383 [4.5%])</th></tr><tr><th>aOR (95% CI)<sup>a</sup></th><th>P value</th><th>aOR (95% CI)<sup>a</sup></th><th>P value</th><th>aOR (95% CI)<sup>a</sup></th><th>P value</th></tr></thead><tbody><tr><td>Age, continuous (10-y decrease)</td><td>1.10 (1.05-1.15)</td><td>&lt;.001</td><td>1.14 (1.07-1.22)</td><td>&lt;.001</td><td>1.20 (1.08-1.34)</td><td>&lt;.001</td></tr><tr><td>Body mass index</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Overweight vs lean</td><td>1.42 (1.24-1.64)</td><td>&lt;.001</td><td>1.90 (1.60-2.26)</td><td>&lt;.001</td><td>2.19 (1.66-2.88)</td><td>&lt;.001</td></tr><tr><td>Obesity vs lean</td><td>1.18 (1.05-1.33)</td><td>.005</td><td>1.25 (1.07-1.46)</td><td>.005</td><td>1.29 (0.99-1.68)</td><td>.06</td></tr><tr><td>Physical activity, sufficiently vs insufficiently active</td><td>0.86 (0.78-0.95)</td><td>.003</td><td>0.84 (0.74-0.96)</td><td>.01</td><td>0.75 (0.60-0.93)</td><td>.008</td></tr><tr><td>Smoking behavior</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Current vs never smoker</td><td>1.09 (0.97-1.23)</td><td>.14</td><td>1.16 (0.99-1.36)</td><td>.07</td><td>1.22 (0.93-1.60)</td><td>.15</td></tr><tr><td>Former vs never smoker</td><td>1.40 (1.22-1.62)</td><td>&lt;.001</td><td>2.15 (1.81-2.55)</td><td>&lt;.001</td><td>2.22 (1.69-2.93)</td><td>&lt;.001</td></tr><tr><td>Alcohol behavior, daily vs less than daily</td><td>1.06 (0.91-1.22)</td><td>.45</td><td>0.99 (0.82-1.20)</td><td>.90</td><td>1.26 (0.93-1.70)</td><td>.14</td></tr><tr><td>Charlson Comorbidity Index score, ≥1 vs 0</td><td>1.24 (1.09-1.41)</td><td>.001</td><td>1.57 (1.34-1.84)</td><td>&lt;.001</td><td>2.11 (1.65-2.69)</td><td>&lt;.001</td></tr><tr><td>Marital status, partnered vs not</td><td>0.98 (0.86-1.11)</td><td>.72</td><td>1.01 (0.86-1.19)</td><td>.88</td><td>0.69 (0.54-0.88)</td><td>.003</td></tr><tr><td>Monthly household income, &lt;€3000 vs ≥€3000<sup>b</sup></td><td>1.14 (1.02-1.27)</td><td>.02</td><td>1.50 (1.30-1.73)</td><td>&lt;.001</td><td>2.09 (1.62-2.70)</td><td>&lt;.001</td></tr><tr><td>Breast cancer stage</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>II vs I</td><td>1.07 (0.95-1.22)</td><td>.27</td><td>1.09 (0.95-1.29)</td><td>.30</td><td>1.18 (0.89-1.56)</td><td>.25</td></tr><tr><td>III vs I</td><td>1.07 (0.86-1.34)</td><td>.53</td><td>1.05 (0.79-1.40)</td><td>.72</td><td>1.26 (0.80-1.99)</td><td>.31</td></tr><tr><td>Breast cancer surgery, mastectomy vs partial breast surgery</td><td>1.07 (0.93-1.23)</td><td>.33</td><td>0.93 (0.78-1.11)</td><td>.41</td><td>0.96 (0.72-1.28)</td><td>.79</td></tr><tr><td>Axillary surgery, axillary dissection vs sentinel node</td><td>1.03 (0.90-1.18)</td><td>.66</td><td>1.07 (0.90-1.26)</td><td>.47</td><td>1.08 (0.82-1.44)</td><td>.58</td></tr><tr><td>Adjuvant chemotherapy, yes vs no</td><td>1.20 (1.06-1.36)</td><td>.005</td><td>1.35 (1.14-1.60)</td><td>&lt;.001</td><td>1.43 (1.08-1.90)</td><td>.01</td></tr><tr><td>Adjuvant radiotherapy, yes vs no</td><td>1.15 (0.94-1.40)</td><td>.18</td><td>0.84 (0.65-1.08)</td><td>.18</td><td>0.99 (0.64-1.53)</td><td>.97</td></tr><tr><td>Adjuvant endocrine therapy, yes vs no</td><td>1.20 (1.06-1.38)</td><td>.005</td><td>1.47 (1.23-1.76)</td><td>&lt;.001</td><td>0.99 (0.76-1.31)</td><td>.98</td></tr><tr><td>Adjuvant anti-human epidermal growth factor receptor-2 therapy, yes vs no</td><td>0.92 (0.78-1.08)</td><td>.30</td><td>1.08 (0.88-1.32)</td><td>.47</td><td>0.90 (0.64-1.27)</td><td>.55</td></tr></tbody></table>

Abbreviation: aOR, adjusted odds ratio.

with trajectory membership revealed associations similar to those found in the overall cohort among patients treated with and without adjuvant chemotherapy (Figure, panels B and C).

Discussion

This cohort study identified factors associated with QOL deterioration, including actionable psychosocial and lifestyle-related factors. Limitations of this study include some attrition in responding to the questionnaires over time and the fact that changes in behavior across time were not dynamically assessed. Nevertheless, our results could be used to facilitate the creation of personalized, proactive, and preventive supportive care pathways¹,⁴ by targeting at-risk patients at diagnosis.² The efficacy of such pathways to prevent QOL deterioration, as well as the best implementation and care delivery model, should be investigated.

ARTICLE INFORMATION

Accepted for Publication: January 9, 2024.

Published: February 29, 2024. doi:10.1001/jamanetworkopen.2024.0688

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<footnote>a aORs reflect results of multinomial regression for the overall cohort (8449 observations used; reference is excellent, 3889 observations [46.0%]).</footnote>

<footnote>b As of February 1, 2024, €1 = $1.09 US.</footnote>
**Open Access:** This is an open access article distributed under the terms of the CC-BY License. © 2024 Franzoi MA et al. JAMA Network Open.

**Corresponding Author:** Ines Vaz-Luis, MD, PhD, Department for the Organization of Patient Pathways, Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France (ines-maria.vaz-duarte-luis@gustaveroussy.fr).

**Author Affiliations:** Cancer Survivorship Group, INSERM Unit 981, Molecular Predictors and New Targets in Oncology, Gustave Roussy, Villejuif, France (Franzoi, Di Meglio, Gillanders, Vaz-Luis); Department for the Organization of Patient Pathways, Gustave Roussy, Villejuif, France (Franzoi, Vaz-Luis); Service de Biostatistique et d'Epidémiologie, Oncostat Inserm U1018, Université Paris-Saclay, Equipe Labellisée Ligue Contre le Cancer, Gustave Roussy, Villejuif, France (Michiels); UNICANCER, Paris, France (Gaudin, Martin).

**Author Contributions:** Drs Franzoi and Vaz-Luis had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

**Concept and design:** Franzoi, Di Meglio, Vaz-Luis.

**Acquisition, analysis, or interpretation of data:** Franzoi, Di Meglio, Michiels, Gillanders, Gaudin, Martin.

**Drafting of the manuscript:** Franzoi, Di Meglio, Michiels, Vaz-Luis.

**Critical review of the manuscript for important intellectual content:** Franzoi, Di Meglio, Gillanders, Gaudin, Martin.

**Statistical analysis:** Di Meglio, Michiels, Vaz-Luis.

**Obtained funding:** Franzoi, Martin, Vaz-Luis.

**Administrative, technical, or material support:** Franzoi, Gillanders, Gaudin, Martin, Vaz-Luis.

**Supervision:** Di Meglio, Vaz-Luis.

**Conflict of Interest Disclosures:** Dr Franzoi reported receiving speaker's fees from Novartis and grants from Resilience Care outside the submitted work. Dr Di Meglio reported receiving personal fees from Kephren outside the submitted work. Dr Michiels reported receiving personal fees from Kedrion, Sensorion, Biophytis, Servier, Yuhan, and Roche outside the submitted work. Dr Vaz-Luis reported receiving speaker's honoraria from Amgen, AstraZeneca, Pfizer, Novartis, and Sandoz; personal fees from Resilience Care; and travel reimbursement from Novartis outside the submitted work. No other disclosures were reported.

**Funding/Support:** The Chronic Toxicities Related to Treatment in Patients With Localized Cancer study is funded by a grant from the French National Research Agency (ANR) to Fabrice André (Principal Investigator), the Prism project (grant ANR-18-IBHU-0002), and the MYPROBE Program (grant ANR-17-RHUS-008). The present work was funded by a Conquer Cancer Breast Cancer Research Foundation Career Development Award for Diversity and Inclusion, supported by Breast Cancer Research Foundation to Dr Franzoi. This research was also supported by the French Government under the Investment for the Future program managed by the ANR (grant ANR-10-COHO-0004).

**Role of the Funder/Sponsor:** The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

**Disclaimer:** Any opinions, findings, and conclusions expressed in this material are those of the authors and do not necessarily reflect those of the American Society of Clinical Oncology, Conquer Cancer, or the Breast Cancer Research Foundation.

**Data Sharing Statement:** See the Supplement.

**Additional Contributions:** Julie Havas, PhD (Gustave Roussy), Barbara Pistilli, MD (Gustave Roussy), Gwenn Menvielle, PhD (Gustave Roussy), Christelle Jouannaud, MD (Institut Jean Godinot), Marion Fournier, MD (Institut Bergonié), Laurence Vanlemmens, MD (Centre Oscar Lambret), Asma Dhaini Merimeche, MD (Institut de Cancerologie de Lorraine), Paul Cottu Aurelie Bertaut, PhD (Institut Curie), Sibille Everhard, PhD (UNICANCER), and Fabrice André, PhD (Gustave Roussy), performed data collection, administrative assistance, and scientific review of this manuscript. They were not compensated for this work.

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2. Mayer DK, Alfano CM. Personalized risk-stratified cancer follow-up care: its potential for healthier survivors, happier clinicians, and lower costs. J Natl Cancer Inst. 2019;111(5):442-448. doi:10.1093/jnci/djy232

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<figure><img src="image_6.png" /></figure>
4. Vaz-Luis I, Cottu P, Mesleard C, et al. UNICANCER: French prospective cohort study of treatment-related chronic toxicity in women with localised breast cancer (CANTO). ESMO Open. 2019;4(5):e000562. doi:10.1136/ esmoopen-2019-000562

SUPPLEMENT.

Data Sharing Statement

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