# Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France

Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, Gaelle Coureau, Pamela Minicozzi, Anne-Sophie Woronoff, Patricia Delafosse, Florence Molinié

<figure><img src="image_1.png" /></figure>

## ► To cite this version:

Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, et al.. Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France. PLoS ONE, 2019, 14 (10), pp.e0224275. 10.1371/journal.pone.0224275. hal-04579588

HAL Id: hal-04579588

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# Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France

Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, Gaelle Coureau, Pamela Minicozzi, Anne-Sophie Woronoff, Patricia Delafosse, Florence Molinié

<figure><img src="image_1.png" /></figure>

## ► To cite this version:

Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, et al.. Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France. PLoS ONE, 2019, 14 (10), pp.e0224275. 10.1371/journal.pone.0224275. hal-04579588

HAL Id: hal-04579588

https://hal.science/hal-04579588v1

Submitted on 17 May 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
RESEARCH ARTICLE

# Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France

Anne Cowppli-Bony<sup>1,2,3*</sup>, Brigitte Trétarre<sup>3,4</sup>, Emilie Marrer<sup>3,5●</sup>, Gautier Defossez<sup>3,6●</sup>, Laetitia Daubisse-Marliac<sup>3,7●</sup>, Gaelle Coureau<sup>3,8●</sup>, Pamela Minicozzi<sup>9</sup>, Anne-Sophie Woronoff<sup>3,10●</sup>, Patricia Delafosse<sup>3,11●</sup>, Florence Molinié<sup>1,2,3</sup>, for the FRANCIM network<sup>3||</sup>

<figure><img src="image_3.png" /></figure>

1. Loire-Atlantique Vendee Cancer Registry, Nantes, France, 2. SIRIC ILIAD INCa-DGOSInserm_12558, CHU Nantes, Nantes, France, 3. French Network of Cancer Registries (FRANCIM), Toulouse, France, 4. Hérault Cancer Registry, Montpellier, France, 5. Haut-Rhin Cancer Registry, Mulhouse, France, 6. Poitou-Charentes Cancer Registry, Poitiers, France, 7. Tarn Cancer Registry, Albi, France, 8. Gironde Cancer Registry, Bordeaux, France, 9. Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, 10. Doubs and Belfort Territory Cancer Registry, Besançon, France, 11. Isère Cancer Registry, Grenoble, France

● These authors contributed equally to this work.

|| Membership of the FRANCIM group is provided in the Acknowledgments.

* anne.cowpplibony@chu-nantes.fr

<figure><img src="image_4.png" /></figure>

OPEN ACCESS

**Citation:** Cowppli-Bony A, Trétarre B, Marrer E, Defossez G, Daubisse-Marliac L, Coureau G, et al. (2019) Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France. PLoS ONE 14(10): e0224275. https://doi.org/10.1371/journal.pone.0224275

**Editor:** Hakan Buyukhatipoglu, Harran Universitesi, UNITED STATES

**Received:** July 3, 2019

**Accepted:** October 9, 2019

**Published:** October 23, 2019

**Copyright:** © 2019 Cowppli-Bony et al. This is an open access article distributed under the terms of the [Creative Commons Attribution License](https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

**Data Availability Statement:** Data from this study are available upon request. According to the recommendations of the French National Commission on Information Technologies and Liberties (CNIL) and the General Data Protection Regulation (GDPR), data cannot be shared publicly because they come from cancer registries and contain potentially identifying patient information. For researchers who meet the criteria for access to confidential data, data are available from the Loire-Atlantique Cancer Vendee Registry after the

## Abstract

### Background

The European Society of Breast Cancer Specialists (EUSOMA), which aims to standardize the quality of patient care in Europe, has defined quality indicators (QIs) for breast cancer (BC) care to assess compliance to current care standards. These QIs are a useful tool to evaluate care organizations. Only population-based studies are able to assess health system performance in “real-life” situations. This population-based study aimed to describe compliance with several EUSOMA QIs overall and according to patient and organizational factors in France.

### Methods

1 560 adult women with primary invasive non-metastatic BC diagnosed in 2012 were randomly selected among all incident BC from 16 French geographical areas covered by cancer registries. Twelve EUSOMA QIs were selected regarding diagnosis, treatment and staging.

### Results

The minimum standard as proposed by EUSOMA was met for nine QIs related to pre-operative definitive diagnosis, multidisciplinary discussion and treatment (single surgery, breast conserving surgery (BCS) for small BC (<3cm), radiotherapy after BCS or mastectomy for regional BC (pN≥2a), hormonotherapy, adjuvant chemotherapy and trastuzumab). Low compliance was observed for sentinel lymph node biopsy (SLNB) and staging imaging.
RESEARCH ARTICLE

# Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France

Anne Cowppli-Bony<sup>1,2,3*</sup>, Brigitte Trétarre<sup>3,4</sup>, Emilie Marrer<sup>3,5</sup>, Gautier Defossez<sup>3,6</sup>, Laetitia Daubisse-Marliac<sup>3,7</sup>, Gaelle Coureau<sup>3,8</sup>, Pamela Minicozzi<sup>9</sup>, Anne-Sophie Woronoff<sup>3,10</sup>, Patricia Delafosse<sup>3,11</sup>, Florence Molinie<sup>1,2,3</sup>, for the FRANCIM network<sup>3†</sup>

<figure><img src="image_3.png" /></figure>

1. Loire-Atlantique Vendee Cancer Registry, Nantes, France, 2. SIRIC ILIAD INCa-DGOSInserm_12558, CHU Nantes, Nantes, France, 3. French Network of Cancer Registries (FRANCIM), Toulouse, France, 4. Hérault Cancer Registry, Montpellier, France, 5. Haut-Rhin Cancer Registry, Mulhouse, France, 6. Poitou-Charentes Cancer Registry, Poitiers, France, 7. Tarn Cancer Registry, Albi, France, 8. Gironde Cancer Registry, Bordeaux, France, 9. Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, 10. Doubs and Belfort Territory Cancer Registry, Besançon, France, 11. Isère Cancer Registry, Grenoble, France

© These authors contributed equally to this work.

† Membership of the FRANCIM group is provided in the Acknowledgments.

* anne.cowpplibony@chu-nantes.fr

<figure><img src="image_4.png" /></figure>

OPEN ACCESS

**Citation:** Cowppli-Bony A, Trétarre B, Marrer E, Defossez G, Daubisse-Marliac L, Coureau G, et al. (2019) Compliance with clinical guidelines for breast cancer management: A population-based study of quality-of-care indicators in France. PLoS ONE 14(10): e0224275. https://doi.org/10.1371/journal.pone.0224275

**Editor:** Hakan Buyukhatipoglu, Harran Universitesi, UNITED STATES

**Received:** July 3, 2019

**Accepted:** October 9, 2019

**Published:** October 23, 2019

**Copyright:** © 2019 Cowppli-Bony et al. This is an open access article distributed under the terms of the [Creative Commons Attribution License](https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

**Data Availability Statement:** Data from this study are available upon request. According to the recommendations of the French National Commission on Information Technologies and Liberties (CNIL) and the General Data Protection Regulation (GDPR), data cannot be shared publicly because they come from cancer registries and contain potentially identifying patient information. For researchers who meet the criteria for access to confidential data, data are available from the Loire-Atlantique Cancer Vendee Registry after the

## Abstract

### Background

The European Society of Breast Cancer Specialists (EUSOMA), which aims to standardize the quality of patient care in Europe, has defined quality indicators (QIs) for breast cancer (BC) care to assess compliance to current care standards. These QIs are a useful tool to evaluate care organizations. Only population-based studies are able to assess health system performance in “real-life” situations. This population-based study aimed to describe compliance with several EUSOMA QIs overall and according to patient and organizational factors in France.

### Methods

1 560 adult women with primary invasive non-metastatic BC diagnosed in 2012 were randomly selected among all incident BC from 16 French geographical areas covered by cancer registries. Twelve EUSOMA QIs were selected regarding diagnosis, treatment and staging.

### Results

The minimum standard as proposed by EUSOMA was met for nine QIs related to pre-operative definitive diagnosis, multidisciplinary discussion and treatment (single surgery, breast conserving surgery (BCS) for small BC (<3cm), radiotherapy after BCS or mastectomy for regional BC (pN≥2a), hormonotherapy, adjuvant chemotherapy and trastuzumab). Low compliance was observed for sentinel lymph node biopsy (SLNB) and staging imaging.
agreement of all participating registries. Data requests may be sent to Loire-Atlantique Vendee Cancer Registry (registre4485@chu-nantes.fr) and FRANCIM network (francim.crct@inserm.fr).

**Funding:** This study was partly supported for data collection by a grant from the French National Cancer Institute (INCa), related to the European study HIGHCARE Transcan Eranet JTC-2013 (http://www.hrstudies.eu/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

**Competing interests:** The authors have declared that no competing interests exist.

Adherence to guidelines was usually lower in older patients and in patients with comorbidities. Multidisciplinary discussion was positively related to adherence to guidelines for diagnosis, staging practices (SNLB, imaging) and systemic treatments. Compliance also varied by area of residence and by place of first treatment.

## Conclusion

This study provides the first current, comprehensive overview of BC quality care at a population level in France. The guidelines were correctly applied in percentage satisfying the EUSOMA standards for the diagnosis and treatment of BC, although staging practices (SNLB, imaging) can be improved. These results highlight the need for continuous measurement of adherence to guidelines to improve BC care.

## Introduction

Breast cancer (BC) is the most commonly diagnosed cancer and leading cause of cancer death in women worldwide [1]. In France, 52621 women were diagnosed with BC in 2012, resulting in 11 780 deaths according to national estimates from cancer registries [2].

To ensure optimal BC care for all patients, clinical practice guidelines have been developed by health organizations and oncology societies [3]. The European Society of Breast Cancer Specialists (EUSOMA), which aims to standardize the quality of patient care in Europe, has defined 33 quality indicators (QIs) to assess compliance to current care standards [4]. Similar QIs have been defined in the US [5]. These indicators may be useful for identifying gaps and areas for quality improvement at local and national levels.

In France, cancer care is delivered by multiple providers, including private fee-for-service physicians, public hospitals and private (non-profit-making and profit-making) hospitals. Each patient is free to choose his physician and his health care facility for care and benefits from a full medical coverage for cancer guaranteeing free access to cancer care.

Population-based cancer registries provide non-biased information on cancer management and are potentially able to assess health system performance, especially regarding the application of guidelines. To our knowledge, no population-based study on QIs for BC management has been conducted in France.

The present population-based study aimed to assess the quality of non-metastatic BC management in France by evaluating compliance with several EUSOMA QIs overall and according to patient and organizational factors. We also described reasons for non-compliant practices.

## Materials and methods

### Population

Data were provided by all French population-based cancer registries of the FRANCIM network, covering 22% of the French population: Bas-Rhin, Calvados, Côte d'Or, Doubs, Haut-Rhin, Haute-Vienne, Hérault, Gironde, Isère, Lille area, Loire-Atlantique, Manche, Poitou-Charentes, Somme, Tarn and Vendée. FRANCIM cancer registries record all new cases of cancer from residents in a geographic area (departement, region or city). The quality and completeness of registry data are certified every five years by the national Evaluation Committee of Registries.
agreement of all participating registries. Data requests may be sent to Loire-Atlantique Vendee Cancer Registry (registre4485@chu-nantes.fr) and FRANCIM network (francim.crct@inserm.fr).

**Funding:** This study was partly supported for data collection by a grant from the French National Cancer Institute (INCa), related to the European study HIGHCARE Transcan Eranet JTC-2013 (http://www.hrstudies.eu/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

**Competing interests:** The authors have declared that no competing interests exist.

Adherence to guidelines was usually lower in older patients and in patients with comorbidities. Multidisciplinary discussion was positively related to adherence to guidelines for diagnosis, staging practices (SNLB, imaging) and systemic treatments. Compliance also varied by area of residence and by place of first treatment.

## Conclusion

This study provides the first current, comprehensive overview of BC quality care at a population level in France. The guidelines were correctly applied in percentage satisfying the EUSOMA standards for the diagnosis and treatment of BC, although staging practices (SNLB, imaging) can be improved. These results highlight the need for continuous measurement of adherence to guidelines to improve BC care.

## Introduction

Breast cancer (BC) is the most commonly diagnosed cancer and leading cause of cancer death in women worldwide [1]. In France, 52621 women were diagnosed with BC in 2012, resulting in 11 780 deaths according to national estimates from cancer registries [2].

To ensure optimal BC care for all patients, clinical practice guidelines have been developed by health organizations and oncology societies [3]. The European Society of Breast Cancer Specialists (EUSOMA), which aims to standardize the quality of patient care in Europe, has defined 33 quality indicators (QIs) to assess compliance to current care standards [4]. Similar QIs have been defined in the US [5]. These indicators may be useful for identifying gaps and areas for quality improvement at local and national levels.

In France, cancer care is delivered by multiple providers, including private fee-for-service physicians, public hospitals and private (non-profit-making and profit-making) hospitals. Each patient is free to choose his physician and his health care facility for care and benefits from a full medical coverage for cancer guaranteeing free access to cancer care.

Population-based cancer registries provide non-biased information on cancer management and are potentially able to assess health system performance, especially regarding the application of guidelines. To our knowledge, no population-based study on QIs for BC management has been conducted in France.

The present population-based study aimed to assess the quality of non-metastatic BC management in France by evaluating compliance with several EUSOMA QIs overall and according to patient and organizational factors. We also described reasons for non-compliant practices.

## Materials and methods

### Population

Data were provided by all French population-based cancer registries of the FRANCIM network, covering 22% of the French population: Bas-Rhin, Calvados, Côte d'Or, Doubs, Haut-Rhin, Haute-Vienne, Hérault, Gironde, Isère, Lille area, Loire-Atlantique, Manche, Poitou-Charentes, Somme, Tarn and Vendée. FRANCIM cancer registries record all new cases of cancer from residents in a geographic area (departement, region or city). The quality and completeness of registry data are certified every five years by the national Evaluation Committee of Registries.
Approximately 100 adult women (≥18 years) with primary BC diagnosed in 2012 were ran-
domly sampled from each registry to compile a large representative sample (n = 1 855).
Regarding the sampling procedure, each registry first selected days and months of birth and
then patients born those days were systematically included in the study. Sampled patients rep-
resented 13% of all the BC women diagnosed in 2012 in FRANCIM registries. Each cancer reg-
istry contributed equally (i.e. regardless of the size of the geographical area covered) to the
study sample.

Only women with carcinomas were included. Patients who presented prior in situ or inva-
sive breast carcinoma were also excluded. This study considered 1 560 women with non-meta-
static invasive BC after excluding in situ and metastatic cancers.

Data collection

In addition to data routinely collected by registries, extensive information was collected from medical records: mode of detection, comorbidities, tumor characteristics at diagnosis (clinical and pathological TNM stages, Scarff-Bloom-Richardson (SBR) grade, estrogen (ER) and progesterone (PR) receptor status and human epidermal growth factor receptor-2 (HER2) status), staging imaging and therapeutic management.

According to TNM Classification of Malignant Tumours (7th edition), stage was defined from pathological stage or from clinical stage in case of neoadjuvant or non-surgical treatment. A phenotypic subtype was defined with hormonal and HER2 status according to the international classification on molecular subtypes of BC [6].

Outcome measures

Twelve QIs were selected considering various aspects of care: diagnosis (pre-operative diagno-
sis (QI_3b)), treatment (multidisciplinary discussion (QI_8), appropriate surgical approach
(QI_9a), post-operative radiotherapy (QIs_10a/b), avoidance of overtreatment (QIs_11a/c),
and appropriate systemic treatment (QIs_12_13a/b)) and staging procedures (QIs_14a/b) [4].
The most relevant QIs were selected based on the purpose of the study and available data. The
last updated (2017) EUSOMA QIs [4] were used instead of QIs from 2010 [7]. The QIs selected
have similar definitions between 2010 and 2017 and reflect the French 2012 guidelines.

Statistical analysis

The outcome measure was the proportion of patients treated in accordance with guidelines for each indicator with its 95% confidence interval (CI). Appropriate patient selection was used for each QI. Patients with missing data on the variables of interest for a specific indicator were excluded from analyses. Considering the complex management of elderly patients, EUSOMA recently proposed the exclusion of older patients (≥70) from analyses in case of low adherence to QIs_10_12_13 [4]. Only QI_13a required application of this recommendation in this study.

Compliance with each QI was compared between patient groups stratified by age (<50, 50-74, and ≥75 years), Charlson comorbidity index [8] (characterized as 0, 1 or ≥2), place of first treatment delivery (grouped into four categories: comprehensive cancer centers (CCC), teaching hospitals (TH), public and private hospitals), multidisciplinary discussion and geographical area of residence covered by the registries. Comparisons of compliance between groups were made using two-sided Chi-square or Fisher's exact tests (in case of low numbers). Analyses were performed using STATA/IC 14.
Approximately 100 adult women (≥18 years) with primary BC diagnosed in 2012 were ran-
domly sampled from each registry to compile a large representative sample (n = 1 855).
Regarding the sampling procedure, each registry first selected days and months of birth and
then patients born those days were systematically included in the study. Sampled patients rep-
resented 13% of all the BC women diagnosed in 2012 in FRANCIM registries. Each cancer reg-
istry contributed equally (i.e. regardless of the size of the geographical area covered) to the
study sample.

Only women with carcinomas were included. Patients who presented prior in situ or inva-
sive breast carcinoma were also excluded. This study considered 1 560 women with non-meta-
static invasive BC after excluding in situ and metastatic cancers.

**Data collection**

In addition to data routinely collected by registries, extensive information was collected from medical records: mode of detection, comorbidities, tumor characteristics at diagnosis (clinical and pathological TNM stages, Scarff-Bloom-Richardson (SBR) grade, estrogen (ER) and progesterone (PR) receptor status and human epidermal growth factor receptor-2 (HER2) status), staging imaging and therapeutic management.

According to TNM Classification of Malignant Tumours (7th edition), stage was defined from pathological stage or from clinical stage in case of neoadjuvant or non-surgical treatment. A phenotypic subtype was defined with hormonal and HER2 status according to the international classification on molecular subtypes of BC [6].

**Outcome measures**

Twelve QIs were selected considering various aspects of care: diagnosis (pre-operative diagno-
sis (QI_3b)), treatment (multidisciplinary discussion (QI_8), appropriate surgical approach
(QI_9a), post-operative radiotherapy (QIs_10a/b), avoidance of overtreatment (QIs_11a/c),
and appropriate systemic treatment (QIs_12_13a/b)) and staging procedures (QIs_14a/b) [4].
The most relevant QIs were selected based on the purpose of the study and available data. The
last updated (2017) EUSOMA QIs [4] were used instead of QIs from 2010 [7]. The QIs selected
have similar definitions between 2010 and 2017 and reflect the French 2012 guidelines.

**Statistical analysis**

The outcome measure was the proportion of patients treated in accordance with guidelines for each indicator with its 95% confidence interval (CI). Appropriate patient selection was used for each QI. Patients with missing data on the variables of interest for a specific indicator were excluded from analyses. Considering the complex management of elderly patients, EUSOMA recently proposed the exclusion of older patients (≥70) from analyses in case of low adherence to QIs_10_12_13 [4]. Only QI_13a required application of this recommendation in this study.

Compliance with each QI was compared between patient groups stratified by age (<50, 50-74, and ≥75 years), Charlson comorbidity index [8] (characterized as 0, 1 or ≥2), place of first treatment delivery (grouped into four categories: comprehensive cancer centers (CCC), teaching hospitals (TH), public and private hospitals), multidisciplinary discussion and geographical area of residence covered by the registries. Comparisons of compliance between groups were made using two-sided Chi-square or Fisher's exact tests (in case of low numbers). Analyses were performed using STATA/IC 14.
## Ethics statement

All FRANCIM cancer registries are approved by the French National Commission on Information Technologies and Liberties (CNIL) to collect nominative data on cancer patients without informed consent, for research purposes and in the strictest confidentiality. However, each cancer patient living in a geographic area covered by a registry is informed that his data can be recorded in the registry database and that he can oppose this registration. Only fully anonymized data are published.

## Results

The characteristics of 1 560 women are presented in Table 1 (mean age = 61.2 years; range = 22–95). Women were often diagnosed at stage I and underwent first-line surgery (86.3%), mainly breast conserving surgery (BCS) (74.0%).

As shown in Table 2, nine QI related to diagnosis and treatment achieved the minimum EUSOMA standards, whereas three QI for compliance were lower than the minimum standards.

Very high adherence to recommendations (above target standards) was found for five QIs (QIs_3b_10a_12_13a/b). The reasons for non-compliance are described below.

* QI_3b (pre-operative histological/cytological diagnosis): Of 38 women without pre-operative diagnosis (non-compliance rate of 2.4%), 34 women underwent surgery as first-line treatment. Four women had no histological diagnosis or biopsy after first hormonal treatment.

* QI_10a (radiotherapy after BCS) and QI_12 (endocrine therapy): Non-compliance (2.2% and 7.0% respectively) was mostly due to physician or patient choice (Table 3).

* QI_13a (adjuvant chemotherapy): Despite general low adherence (82.6%), adherence became very high (95.8%) when older patients (≥70 years) were excluded. Chemotherapy was often not performed because of medical choice or contraindication (Table 3).

* QI_13b (adjuvant trastuzumab): Only two women (ages 45 and 68 years old) did not receive adjuvant trastuzumab among 104 eligible cases (non-compliance rate of 1.9%).

High adherence to recommendations (between minimum and target standards) was observed for four QIs:

* QI_8 (multidisciplinary discussion): Medical files of 37 women were not examined within a multidisciplinary team meeting (MTM) (non-compliance rate of 2.4%). These women received mainly hormonotherapy alone (48.6%), whereas the others had surgery (alone (8.1%) or with adjuvant treatments (24.3%)), neoadjuvant therapy (2.7%) or no treatment (16.2%).

* QI_9a (single surgery): A total of 185 women underwent several breast operations (non-compliance rate of 12.5%): 164 had a second operation (half were BCS), whereas 21 had three surgeries.

* QI_10b (postmastectomy radiotherapy for BC with $pN \ge 2a$): Four women (non-compliance rate of 6.8%) did not have radiotherapy because of patient factors (Table 3).

* QI_11c (BCS for small BC, defined as histological tumor size <30mm): Among 225 women with small BC who underwent mastectomy (non-compliance rate of 19.2%), 28.0% had a first BCS with positive margins and 58.2% had a multicentric or overlapping tumor, which is an indication to perform mastectomy.
**Ethics statement**

All FRANCIM cancer registries are approved by the French National Commission on Information Technologies and Liberties (CNIL) to collect nominative data on cancer patients without informed consent, for research purposes and in the strictest confidentiality. However, each cancer patient living in a geographic area covered by a registry is informed that his data can be recorded in the registry database and that he can oppose this registration. Only fully anonymized data are published.

**Results**

The characteristics of 1 560 women are presented in Table 1 (mean age = 61.2 years; range = 22–95). Women were often diagnosed at stage I and underwent first-line surgery (86.3%), mainly breast conserving surgery (BCS) (74.0%).

As shown in Table 2, nine QI related to diagnosis and treatment achieved the minimum EUSOMA standards, whereas three QI for compliance were lower than the minimum standards.

Very high adherence to recommendations (above target standards) was found for five QIs (QIs_3b_10a_12_13a/b). The reasons for non-compliance are described below.

* QI_3b (pre-operative histological/cytological diagnosis): Of 38 women without pre-operative diagnosis (non-compliance rate of 2.4%), 34 women underwent surgery as first-line treatment. Four women had no histological diagnosis or biopsy after first hormonal treatment.

* QI_10a (radiotherapy after BCS) and QI_12 (endocrine therapy): Non-compliance (2.2% and 7.0% respectively) was mostly due to physician or patient choice (Table 3).

* QI_13a (adjuvant chemotherapy): Despite general low adherence (82.6%), adherence became very high (95.8%) when older patients (≥70 years) were excluded. Chemotherapy was often not performed because of medical choice or contraindication (Table 3).

* QI_13b (adjuvant trastuzumab): Only two women (ages 45 and 68 years old) did not receive adjuvant trastuzumab among 104 eligible cases (non-compliance rate of 1.9%).

High adherence to recommendations (between minimum and target standards) was observed for four QIs:

* QI_8 (multidisciplinary discussion): Medical files of 37 women were not examined within a multidisciplinary team meeting (MTM) (non-compliance rate of 2.4%). These women received mainly hormonotherapy alone (48.6%), whereas the others had surgery (alone (8.1%) or with adjuvant treatments (24.3%)), neoadjuvant therapy (2.7%) or no treatment (16.2%).

* QI_9a (single surgery): A total of 185 women underwent several breast operations (non-compliance rate of 12.5%): 164 had a second operation (half were BCS), whereas 21 had three surgeries.

* QI_10b (postmastectomy radiotherapy for BC with $pN \ge 2a$): Four women (non-compliance rate of 6.8%) did not have radiotherapy because of patient factors (Table 3).

* QI_11c (BCS for small BC, defined as histological tumor size <30mm): Among 225 women with small BC who underwent mastectomy (non-compliance rate of 19.2%), 28.0% had a first BCS with positive margins and 58.2% had a multicentric or overlapping tumor, which is an indication to perform mastectomy.
<table><caption>Table 1. Characteristics of patients diagnosed with non-metastatic invasive breast cancers in 2012 in France (N = 1 560).</caption><thead><tr><th>Characteristics</th><th>N</th><th>%</th></tr></thead><tbody><tr><td><strong>Age at diagnosis (years)</strong></td><td></td><td></td></tr><tr><td>&lt; 50</td><td>340</td><td>21.8</td></tr><tr><td>50-74</td><td>933</td><td>59.8</td></tr><tr><td>≥ 75</td><td>287</td><td>18.4</td></tr><tr><td><strong>Charlson comorbidity index</strong></td><td></td><td></td></tr><tr><td>0</td><td>1 128</td><td>72.3</td></tr><tr><td>1</td><td>232</td><td>14.9</td></tr><tr><td>≥2</td><td>186</td><td>11.9</td></tr><tr><td>Unknown</td><td>14</td><td>0.9</td></tr><tr><td><strong>Mode of detection</strong></td><td></td><td></td></tr><tr><td>Organized/opportunistic screening</td><td>793</td><td>50.8</td></tr><tr><td>Clinical diagnosis</td><td>730</td><td>46.8</td></tr><tr><td>Other</td><td>22</td><td>1.4</td></tr><tr><td>Unknown</td><td>15</td><td>1.0</td></tr><tr><td><strong>SBR grade</strong></td><td></td><td></td></tr><tr><td>1</td><td>384</td><td>24.6</td></tr><tr><td>2</td><td>781</td><td>50.1</td></tr><tr><td>3</td><td>366</td><td>23.5</td></tr><tr><td>Unknown</td><td>29</td><td>1.9</td></tr><tr><td><strong>Phenotypic subtype</strong></td><td></td><td></td></tr><tr><td>Luminal A/B (ER+ and/or PR+, HER2 -)</td><td>1 198</td><td>76.8</td></tr><tr><td>Luminal A/B-HER2 (ER+ and/or PR+, HER2 +)</td><td>120</td><td>7.7</td></tr><tr><td>HER2 (ER-, PR-, HER2+)</td><td>78</td><td>5.0</td></tr><tr><td>Triple negative (ER-, PR-, HER2-)</td><td>148</td><td>9.5</td></tr><tr><td>Undetermined</td><td>16</td><td>1.0</td></tr><tr><td><strong>Stage at diagnosis</strong></td><td></td><td></td></tr><tr><td>IA (T1-N0-M0)</td><td>755</td><td>48.4</td></tr><tr><td>IB (T0/1-N1mi-M0)</td><td>42</td><td>2.7</td></tr><tr><td>IIA (T0/1-N1-M0 or T2-N0-M0)</td><td>366</td><td>23.5</td></tr><tr><td>IIB (T2-N1-M0 or T3-N0-M0)</td><td>196</td><td>12.6</td></tr><tr><td>IIIA (T0/1/2-N2-M0 or T3-N1/2-M0)</td><td>95</td><td>6.1</td></tr><tr><td>IIIB (T4-N0/1/2-M0)</td><td>57</td><td>3.6</td></tr><tr><td>IIIC (anyT-N3-M0)</td><td>32</td><td>2.1</td></tr><tr><td>Unknown (T or N missing, M0)</td><td>17</td><td>1.1</td></tr><tr><td><strong>Treatment</strong></td><td></td><td></td></tr><tr><td>Surgery (+/- HT)</td><td>111</td><td>7.1</td></tr><tr><td>Surgery with adjuvant RT (+/- HT)</td><td>695</td><td>44.6</td></tr><tr><td>Surgery with adjuvant CT + RT (+/- HT)</td><td>496</td><td>31.8</td></tr><tr><td>Surgery with adjuvant CT (+/- HT)</td><td>43</td><td>2.8</td></tr><tr><td>Neoadjuvant therapy (CT or HT) and surgery</td><td>140</td><td>9.0</td></tr><tr><td>Other treatments (CT, RT, HT) without surgery</td><td>58</td><td>3.7</td></tr><tr><td>None</td><td>14</td><td>0.9</td></tr><tr><td>Unknown</td><td>3</td><td>0.2</td></tr><tr><td><strong>Place of first treatment delivery</strong></td><td></td><td></td></tr><tr><td>Public hospital</td><td>222</td><td>14.2</td></tr><tr><td>Private hospital</td><td>708</td><td>45.4</td></tr></tbody></table>

(Continued)
<table><caption>Table 1. Characteristics of patients diagnosed with non-metastatic invasive breast cancers in 2012 in France (N = 1 560).</caption><thead><tr><th>Characteristics</th><th>N</th><th>%</th></tr></thead><tbody><tr><td><strong>Age at diagnosis (years)</strong></td><td></td><td></td></tr><tr><td>&lt; 50</td><td>340</td><td>21.8</td></tr><tr><td>50-74</td><td>933</td><td>59.8</td></tr><tr><td>≥ 75</td><td>287</td><td>18.4</td></tr><tr><td><strong>Charlson comorbidity index</strong></td><td></td><td></td></tr><tr><td>0</td><td>1 128</td><td>72.3</td></tr><tr><td>1</td><td>232</td><td>14.9</td></tr><tr><td>≥2</td><td>186</td><td>11.9</td></tr><tr><td>Unknown</td><td>14</td><td>0.9</td></tr><tr><td><strong>Mode of detection</strong></td><td></td><td></td></tr><tr><td>Organized/opportunistic screening</td><td>793</td><td>50.8</td></tr><tr><td>Clinical diagnosis</td><td>730</td><td>46.8</td></tr><tr><td>Other</td><td>22</td><td>1.4</td></tr><tr><td>Unknown</td><td>15</td><td>1.0</td></tr><tr><td><strong>SBR grade</strong></td><td></td><td></td></tr><tr><td>1</td><td>384</td><td>24.6</td></tr><tr><td>2</td><td>781</td><td>50.1</td></tr><tr><td>3</td><td>366</td><td>23.5</td></tr><tr><td>Unknown</td><td>29</td><td>1.9</td></tr><tr><td><strong>Phenotypic subtype</strong></td><td></td><td></td></tr><tr><td>Luminal A/B (ER+ and/or PR+, HER2 -)</td><td>1 198</td><td>76.8</td></tr><tr><td>Luminal A/B-HER2 (ER+ and/or PR+, HER2 +)</td><td>120</td><td>7.7</td></tr><tr><td>HER2 (ER-, PR-, HER2+)</td><td>78</td><td>5.0</td></tr><tr><td>Triple negative (ER-, PR-, HER2-)</td><td>148</td><td>9.5</td></tr><tr><td>Undetermined</td><td>16</td><td>1.0</td></tr><tr><td><strong>Stage at diagnosis</strong></td><td></td><td></td></tr><tr><td>IA (T1-N0-M0)</td><td>755</td><td>48.4</td></tr><tr><td>IB (T0/1-N1mi-M0)</td><td>42</td><td>2.7</td></tr><tr><td>IIA (T0/1-N1-M0 or T2-N0-M0)</td><td>366</td><td>23.5</td></tr><tr><td>IIB (T2-N1-M0 or T3-N0-M0)</td><td>196</td><td>12.6</td></tr><tr><td>IIIA (T0/1/2-N2-M0 or T3-N1/2-M0)</td><td>95</td><td>6.1</td></tr><tr><td>IIIB (T4-N0/1/2-M0)</td><td>57</td><td>3.6</td></tr><tr><td>IIIC (anyT-N3-M0)</td><td>32</td><td>2.1</td></tr><tr><td>Unknown (T or N missing, M0)</td><td>17</td><td>1.1</td></tr><tr><td><strong>Treatment</strong></td><td></td><td></td></tr><tr><td>Surgery (+/- HT)</td><td>111</td><td>7.1</td></tr><tr><td>Surgery with adjuvant RT (+/- HT)</td><td>695</td><td>44.6</td></tr><tr><td>Surgery with adjuvant CT + RT (+/- HT)</td><td>496</td><td>31.8</td></tr><tr><td>Surgery with adjuvant CT (+/- HT)</td><td>43</td><td>2.8</td></tr><tr><td>Neoadjuvant therapy (CT or HT) and surgery</td><td>140</td><td>9.0</td></tr><tr><td>Other treatments (CT, RT, HT) without surgery</td><td>58</td><td>3.7</td></tr><tr><td>None</td><td>14</td><td>0.9</td></tr><tr><td>Unknown</td><td>3</td><td>0.2</td></tr><tr><td><strong>Place of first treatment delivery</strong></td><td></td><td></td></tr><tr><td>Public hospital</td><td>222</td><td>14.2</td></tr><tr><td>Private hospital</td><td>708</td><td>45.4</td></tr></tbody></table>

(Continued)
<table><caption>**Table 1.** (Continued)</caption><thead><tr><th>Characteristics</th><th>N</th><th>%</th></tr></thead><tbody><tr><td>Teaching hospital</td><td>161</td><td>10.3</td></tr><tr><td>Comprehensive cancer center</td><td>399</td><td>25.6</td></tr><tr><td>Unknown</td><td>70</td><td>4.5</td></tr></tbody></table>

SBR, Scarff-Bloom-Richardson (SBR); ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor-2; CT, chemotherapy; RT, radiotherapy; HT, hormonotherapy.

https://doi.org/10.1371/journal.pone.0224275.t002

Low adherence to recommendations was observed for three QIs:

* **QI_11a (sentinel lymph node biopsy (SLNB))**: Among 279 patients not receiving SNLB (non-compliance rate of 23.8%), 208 had an axillary lymph node dissection (ALND). Other patients received surgery without axillary procedure (n = 21), hormonotherapy alone

<table><caption>**Table 2.** Definition of EUSOMA quality indicators and compliance in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France).</caption><thead><tr><th colspan="2">Definition of EUSOMA QIs</th><th>Minimum / target standards (%)</th><th>Number of eligible cases</th><th colspan="3">Compliance</th><th colspan="2">Missing</th></tr><tr><th></th><th></th><th></th><th></th><th>N</th><th>%</th><th>(95% CI)</th><th>N</th><th>%</th></tr></thead><tbody><tr><td colspan="2"><strong>Diagnosis</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Pre-operative diagnosis</td><td>3b. Proportion of women who had a pre-operative histologically or cytologically definitive diagnosis</td><td>85 / 90</td><td>1 560</td><td>1 522</td><td>97.6</td><td>(96.7-98.3)</td><td>0</td><td></td></tr><tr><td colspan="2"><strong>Surgery and locoregional treatment</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Multidisciplinary discussion</td><td>8. Proportion of patients to be discussed by a multidisciplinary team</td><td>90 / 99</td><td>1 560</td><td>1 491</td><td>97.6</td><td>(96.7-98.3)</td><td>32</td><td>2.1</td></tr><tr><td>Appropriate surgical approach</td><td>9a. Proportion of patients with surgical treatment who received a single (breast) operation for the primary tumor (excluding reconstruction)</td><td>80 / 90</td><td>1 485</td><td>1 300</td><td>87.5</td><td>(85.8-89.2)</td><td>0</td><td></td></tr><tr><td rowspan="2">Post-operative radiotherapy</td><td>10a. Proportion of patients who received post-operative radiotherapy after surgical resection of the primary tumor and appropriate axillary staging/surgery in the framework of BCS</td><td>90 / 95</td><td>969</td><td>945</td><td>97.8</td><td>(96.7-98.6)</td><td>3</td><td>0.3</td></tr><tr><td>10b. Proportion of patients with involvement of axillary lymph nodes (≥pN2a) who received postmastectomy radiotherapy</td><td>90 / 95</td><td>59</td><td>55</td><td>93.2</td><td>(83.5-98.1)</td><td>0</td><td></td></tr><tr><td rowspan="2">Avoidance of overtreatment</td><td>11a. Proportion of patients with a clinically negative axilla (cN0) who had sentinel lymph node biopsy only</td><td>90 / 95</td><td>1 175</td><td>895</td><td>76.2</td><td>(73.7-78.6)</td><td>1</td><td>0.1</td></tr><tr><td>11c. Proportion of patients with BC not greater than 3 cm who underwent BCS as primary treatment</td><td>70 / 85</td><td>1 172</td><td>947</td><td>80.8</td><td>(78.5-83.1)</td><td>0</td><td></td></tr><tr><td colspan="2"><strong>Systemic treatment</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Appropriate endocrine therapy</td><td>12. Proportion of patients with endocrine-sensitive BC who received endocrine therapy</td><td>85 / 90</td><td>1 318</td><td>1 215</td><td>93.0</td><td>(91.5-94.4)</td><td>12</td><td>0.9</td></tr><tr><td rowspan="2">Appropriate chemotherapy and HER2-targeted therapy</td><td>13a. Proportion of patients with ER-(T > 1 cm or N+) BC who received adjuvant chemotherapy</td><td>85 / 95</td><td>139</td><td>114</td><td>82.6</td><td>(75.2-88.5)</td><td>1</td><td>0.7</td></tr><tr><td>(&lt;70 years)</td><td></td><td>96</td><td>92</td><td>95.8</td><td>(89.7-98.9)</td><td>0</td><td></td></tr><tr><td></td><td>13b. Proportion of patients with HER2+ (T > 1 cm or N+) BC treated with chemotherapy who received adjuvant trastuzumab</td><td>85 / 95</td><td>104</td><td>101</td><td>98.1</td><td>(93.2-99.8)</td><td>1</td><td>1.0</td></tr><tr><td colspan="2"><strong>Staging, counseling, follow-up and rehabilitation</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Appropriate staging procedure</td><td>14a. Proportion of women with stage I or primary operable stage II BC who do not undergo baseline-staging tests</td><td>95 / 99</td><td>1 359</td><td>325</td><td>24.7</td><td>(22.4-27.1)</td><td>44</td><td>3.2</td></tr><tr><td>14b. Proportion of women with stage III BC who undergo baseline-staging tests</td><td>95 / 99</td><td>184</td><td>144</td><td>79.1</td><td>(72.5-84.8)</td><td>2</td><td>1.1</td></tr></tbody></table>

Patients with missing values were excluded to calculate compliance per QI. The proportion of missing values indicates the missing values of the variables of interest in the selection that was made for the specific QI.

BC, breast cancer; BCS, breast conserving surgery; ER, estrogen receptor; T, tumor size; N, node involvement.

https://doi.org/10.1371/journal.pone.0224275.t002
<table><caption>**Table 1.** (Continued)</caption><thead><tr><th>Characteristics</th><th>N</th><th>%</th></tr></thead><tbody><tr><td>Teaching hospital</td><td>161</td><td>10.3</td></tr><tr><td>Comprehensive cancer center</td><td>399</td><td>25.6</td></tr><tr><td>Unknown</td><td>70</td><td>4.5</td></tr></tbody></table>

SBR, Scarff-Bloom-Richardson (SBR); ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor-2; CT, chemotherapy; RT, radiotherapy; HT, hormonotherapy.

https://doi.org/10.1371/journal.pone.0224275.t002

Low adherence to recommendations was observed for three QIs:

* **QI_11a (sentinel lymph node biopsy (SLNB))**: Among 279 patients not receiving SNLB (non-compliance rate of 23.8%), 208 had an axillary lymph node dissection (ALND). Other patients received surgery without axillary procedure (n = 21), hormonotherapy alone

<table><caption>**Table 2.** Definition of EUSOMA quality indicators and compliance in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France).</caption><thead><tr><th colspan="2">Definition of EUSOMA QIs</th><th>Minimum / target standards (%)</th><th>Number of eligible cases</th><th colspan="3">Compliance</th><th colspan="2">Missing</th></tr><tr><th></th><th></th><th></th><th></th><th>N</th><th>%</th><th>(95% CI)</th><th>N</th><th>%</th></tr></thead><tbody><tr><td><strong>Diagnosis</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Pre-operative diagnosis</td><td>3b. Proportion of women who had a pre-operative histologically or cytologically definitive diagnosis</td><td>85 / 90</td><td>1 560</td><td>1 522</td><td>97.6</td><td>(96.7-98.3)</td><td>0</td><td></td></tr><tr><td><strong>Surgery and locoregional treatment</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Multidisciplinary discussion</td><td>8. Proportion of patients to be discussed by a multidisciplinary team</td><td>90 / 99</td><td>1 560</td><td>1 491</td><td>97.6</td><td>(96.7-98.3)</td><td>32</td><td>2.1</td></tr><tr><td>Appropriate surgical approach</td><td>9a. Proportion of patients with surgical treatment who received a single (breast) operation for the primary tumor (excluding reconstruction)</td><td>80 / 90</td><td>1 485</td><td>1 300</td><td>87.5</td><td>(85.8-89.2)</td><td>0</td><td></td></tr><tr><td>Post-operative radiotherapy</td><td>10a. Proportion of patients who received post-operative radiotherapy after surgical resection of the primary tumor and appropriate axillary staging/surgery in the framework of BCS</td><td>90 / 95</td><td>969</td><td>945</td><td>97.8</td><td>(96.7-98.6)</td><td>3</td><td>0.3</td></tr><tr><td></td><td>10b. Proportion of patients with involvement of axillary lymph nodes (≥pN2a) who received postmastectomy radiotherapy</td><td>90 / 95</td><td>59</td><td>55</td><td>93.2</td><td>(83.5-98.1)</td><td>0</td><td></td></tr><tr><td>Avoidance of overtreatment</td><td>11a. Proportion of patients with a clinically negative axilla (cN0) who had sentinel lymph node biopsy only</td><td>90 / 95</td><td>1 175</td><td>895</td><td>76.2</td><td>(73.7-78.6)</td><td>1</td><td>0.1</td></tr><tr><td></td><td>11c. Proportion of patients with BC not greater than 3 cm who underwent BCS as primary treatment</td><td>70 / 85</td><td>1 172</td><td>947</td><td>80.8</td><td>(78.5-83.1)</td><td>0</td><td></td></tr><tr><td><strong>Systemic treatment</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Appropriate endocrine therapy</td><td>12. Proportion of patients with endocrine-sensitive BC who received endocrine therapy</td><td>85 / 90</td><td>1 318</td><td>1 215</td><td>93.0</td><td>(91.5-94.4)</td><td>12</td><td>0.9</td></tr><tr><td>Appropriate chemotherapy and HER2-targeted therapy</td><td>13a. Proportion of patients with ER-(T > 1 cm or N+) BC who received adjuvant chemotherapy</td><td>85 / 95</td><td>139</td><td>114</td><td>82.6</td><td>(75.2-88.5)</td><td>1</td><td>0.7</td></tr><tr><td></td><td>(&lt;70 years)</td><td></td><td>96</td><td>92</td><td>95.8</td><td>(89.7-98.9)</td><td>0</td><td></td></tr><tr><td></td><td>13b. Proportion of patients with HER2+ (T > 1 cm or N+) BC treated with chemotherapy who received adjuvant trastuzumab</td><td>85 / 95</td><td>104</td><td>101</td><td>98.1</td><td>(93.2-99.8)</td><td>1</td><td>1.0</td></tr><tr><td><strong>Staging, counseling, follow-up and rehabilitation</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Appropriate staging procedure</td><td>14a. Proportion of women with stage I or primary operable stage II BC who do not undergo baseline-staging tests</td><td>95 / 99</td><td>1 359</td><td>325</td><td>24.7</td><td>(22.4-27.1)</td><td>44</td><td>3.2</td></tr><tr><td></td><td>14b. Proportion of women with stage III BC who undergo baseline-staging tests</td><td>95 / 99</td><td>184</td><td>144</td><td>79.1</td><td>(72.5-84.8)</td><td>2</td><td>1.1</td></tr></tbody></table>

Patients with missing values were excluded to calculate compliance per QI. The proportion of missing values indicates the missing values of the variables of interest in the selection that was made for the specific QI.

BC, breast cancer; BCS, breast conserving surgery; ER, estrogen receptor; T, tumor size; N, node involvement.

https://doi.org/10.1371/journal.pone.0224275.t002
<table><caption>Table 3. Reasons for non-compliance with treatment QIs in patients diagnosed with non-metastatic invasive breast cancers in 2012 (France).</caption><thead><tr><th rowspan="2">Reasons for non-compliance</th><th colspan="2">QI_10a</th><th colspan="2">QI_10b</th><th colspan="2">QI_12</th><th colspan="2">QI_13a</th></tr><tr><th>N</th><th>%</th><th>N</th><th>%</th><th>N</th><th>%</th><th>N</th><th>%</th></tr></thead><tbody><tr><td>Patient refusal</td><td>8</td><td>36.4</td><td>1</td><td>25.0</td><td>28</td><td>30.8</td><td>2</td><td>8.3</td></tr><tr><td>Medical choice</td><td>7</td><td>31.8</td><td>0</td><td>0.0</td><td>44</td><td>48.4</td><td>13</td><td>54.2</td></tr><tr><td>Contraindication</td><td>4</td><td>18.2</td><td>1</td><td>25.0</td><td>8</td><td>8.8</td><td>7</td><td>29.2</td></tr><tr><td>Death</td><td>1</td><td>4.5</td><td>2</td><td>50.0</td><td>4</td><td>4.4</td><td>1</td><td>4.2</td></tr><tr><td>Other (another synchronous cancer)</td><td>2</td><td>9.1</td><td>0</td><td>0.0</td><td>3</td><td>3.3</td><td>0</td><td>0.0</td></tr><tr><td>Unknown</td><td>0</td><td>0.0</td><td>0</td><td>0.0</td><td>4</td><td>4.4</td><td>1</td><td>4.2</td></tr><tr><td>Total of non-compliant cases</td><td>22</td><td>100.0</td><td>4</td><td>100.0</td><td>91</td><td>100.0</td><td>24</td><td>100.0</td></tr></tbody></table>

https://doi.org/10.1371/journal.pone.0224275.t003

(n = 41) or no treatment (n = 9). Compared to compliant cases, non-compliant BCs with ALND had higher T-stage (44.7/38.5% T1/T2 vs 82.9/14.3%), grade (32.2% grade 3 vs 18.0%) and more aggressive phenotypes (5.0/10.6% HER2/triple negative vs 3.0/7.8%).

* QI_14a (staging procedures for stages I-II): Contrary to guidelines, 75.2% of patients at stage I-II underwent at least one test (stage I: 65.8% and stage II: 88.7%). Chest, abdomen and bone were all explored for 72.1% of patients.

* QI_14b (staging procedures for stage III): Only 79.1% of patients at stage III underwent complete work-up. The 38 non-compliant cases had no (7.9%) or incomplete work-up (15.8% and 76.3% with one and two tests, respectively). Most patients (n = 35) received treatments (surgery, hormonotherapy alone or neoadjuvant therapy).

Regarding compliance by age (Fig 1), older patients (≥75) often had significantly lower adherences, except for QIs_12_13b_14a. Higher adherence was observed among older patients for single breast operation (QI_9a), whereas BCS for small BC (QI_11a) was more frequent in the 50-74 age group. Adherence was often higher in patients without comorbidity except for QIs_9a_14a (Fig 2). When medical files were examined within a MTM, compliance was better for preoperative diagnosis (QI_3b: 97.8% vs 89.2% p-Fisher = 0.01), SLNB (QI_11a: 78.0% vs 25.8% p<0.01), hormonotherapy (QI_12: 93.4% vs 83.3% p-Fisher = 0.049) and staging tests for stage III (QI_14b: 81% vs 0%, p-Fisher<0.01). All patients receiving chemotherapy (QI_13a/b) were discussed at MTM. No compliance difference was found for surgery (QI_9a_11c), radiotherapy (QI_10a/b) and staging tests for stage I-II (QI_14a). Compliance differed by place of first treatment for four QIs (Fig 3). It was higher in CCC for pre-operative diagnosis (QI_3b) and staging tests for stage I-II (QI_14a), lower for SLNB in public hospitals (QI_11a) and higher for BCS for small BC in private hospitals (QI_11c). Compliance also varied by geographical area of residence for single surgery, SLNB, BCS, hormonotherapy and staging tests for stage I-II (QIs_9a_11a/c_12_14a) (S1 Fig).

Discussion

The guidelines were correctly applied in percentage satisfying the EUSOMA standards in France for QIs related to diagnosis and treatment of invasive BC. Low adherence to recommendations was observed for SLNB and staging imaging. Adherence to guidelines was usually lower in older patients and patients with comorbidities. Compliance also varied by area of residence, place of first treatment and MTM.

Numerous studies have examined BC care quality. Several studies were conducted before 2003, when guidelines and treatments differed than those currently in use. Out of all recent studies [9-29], the only few conducted at the population level [9-12,16,17,28,29] used recent
<table><caption>Table 3. Reasons for non-compliance with treatment QIs in patients diagnosed with non-metastatic invasive breast cancers in 2012 (France).</caption><thead><tr><th rowspan="2">Reasons for non-compliance</th><th colspan="2">QI_10a</th><th colspan="2">QI_10b</th><th colspan="2">QI_12</th><th colspan="2">QI_13a</th></tr><tr><th>N</th><th>%</th><th>N</th><th>%</th><th>N</th><th>%</th><th>N</th><th>%</th></tr></thead><tbody><tr><td>Patient refusal</td><td>8</td><td>36.4</td><td>1</td><td>25.0</td><td>28</td><td>30.8</td><td>2</td><td>8.3</td></tr><tr><td>Medical choice</td><td>7</td><td>31.8</td><td>0</td><td>0.0</td><td>44</td><td>48.4</td><td>13</td><td>54.2</td></tr><tr><td>Contraindication</td><td>4</td><td>18.2</td><td>1</td><td>25.0</td><td>8</td><td>8.8</td><td>7</td><td>29.2</td></tr><tr><td>Death</td><td>1</td><td>4.5</td><td>2</td><td>50.0</td><td>4</td><td>4.4</td><td>1</td><td>4.2</td></tr><tr><td>Other (another synchronous cancer)</td><td>2</td><td>9.1</td><td>0</td><td>0.0</td><td>3</td><td>3.3</td><td>0</td><td>0.0</td></tr><tr><td>Unknown</td><td>0</td><td>0.0</td><td>0</td><td>0.0</td><td>4</td><td>4.4</td><td>1</td><td>4.2</td></tr><tr><td>Total of non-compliant cases</td><td>22</td><td>100.0</td><td>4</td><td>100.0</td><td>91</td><td>100.0</td><td>24</td><td>100.0</td></tr></tbody></table>

https://doi.org/10.1371/journal.pone.0224275.t003

(n = 41) or no treatment (n = 9). Compared to compliant cases, non-compliant BCs with ALND had higher T-stage (44.7/38.5% T1/T2 vs 82.9/14.3%), grade (32.2% grade 3 vs 18.0%) and more aggressive phenotypes (5.0/10.6% HER2/triple negative vs 3.0/7.8%).

* QI_14a (staging procedures for stages I-II): Contrary to guidelines, 75.2% of patients at stage I-II underwent at least one test (stage I: 65.8% and stage II: 88.7%). Chest, abdomen and bone were all explored for 72.1% of patients.

* QI_14b (staging procedures for stage III): Only 79.1% of patients at stage III underwent complete work-up. The 38 non-compliant cases had no (7.9%) or incomplete work-up (15.8% and 76.3% with one and two tests, respectively). Most patients (n = 35) received treatments (surgery, hormonotherapy alone or neoadjuvant therapy).

Regarding compliance by age (Fig 1), older patients (≥75) often had significantly lower adherences, except for QIs_12_13b_14a. Higher adherence was observed among older patients for single breast operation (QI_9a), whereas BCS for small BC (QI_11a) was more frequent in the 50-74 age group. Adherence was often higher in patients without comorbidity except for QIs_9a_14a (Fig 2). When medical files were examined within a MTM, compliance was better for preoperative diagnosis (QI_3b: 97.8% vs 89.2% p-Fisher = 0.01), SLNB (QI_11a: 78.0% vs 25.8% p<0.01), hormonotherapy (QI_12: 93.4% vs 83.3% p-Fisher = 0.049) and staging tests for stage III (QI_14b: 81% vs 0%, p-Fisher<0.01). All patients receiving chemotherapy (QI_13a/b) were discussed at MTM. No compliance difference was found for surgery (QI_9a_11c), radiotherapy (QI_10a/b) and staging tests for stage I-II (QI_14a). Compliance differed by place of first treatment for four QIs (Fig 3). It was higher in CCC for pre-operative diagnosis (QI_3b) and staging tests for stage I-II (QI_14a), lower for SLNB in public hospitals (QI_11a) and higher for BCS for small BC in private hospitals (QI_11c). Compliance also varied by geographical area of residence for single surgery, SLNB, BCS, hormonotherapy and staging tests for stage I-II (QIs_9a_11a/c_12_14a) (S1 Fig).

Discussion

The guidelines were correctly applied in percentage satisfying the EUSOMA standards in France for QIs related to diagnosis and treatment of invasive BC. Low adherence to recommendations was observed for SLNB and staging imaging. Adherence to guidelines was usually lower in older patients and patients with comorbidities. Compliance also varied by area of residence, place of first treatment and MTM.

Numerous studies have examined BC care quality. Several studies were conducted before 2003, when guidelines and treatments differed than those currently in use. Out of all recent studies [9–29], the only few conducted at the population level [9–12,16,17,28,29] used recent
<figure><img src="image_5.png" /><figcaption>**Fig 1.** Compliance (%) of each QI by age group (<50, 50-74, ≥75 years) in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France). The extent of the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum standard for each QI. *p*: Fisher tests were used for QIs 10a/b and 13a/b.</figcaption></figure>

https://doi.org/10.1371/journal.pone.0224275.g001

data (after 2010) [28,29]. Five studies using EUSOMA QIs [22,24-27] were hospital-based and included patients from voluntary centers (often EUSOMA certified centers [22,24-26]), which may introduce selection biases and overestimate compliance. The assessment of health system performance in BC care requires measuring of compliance in “real-life” situations. In 2019, two population-based studies on EUSOMA QIs for the management of BC diagnosed in 2013 and 2016 were conducted in Slovenia and Norway [28,29]. The results of these studies are difficult to generalize to French patients because of differences between health systems. The French system presents some distinguishing features: the importance of private sector which is
<figure><img src="image_5.png" /><figcaption>**Fig 1.** Compliance (%) of each QI by age group (<50, 50-74, ≥75 years) in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France). The extent of the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum standard for each QI. *p*: Fisher tests were used for QIs 10a/b and 13a/b.</figcaption></figure>

https://doi.org/10.1371/journal.pone.0224275.g001

data (after 2010) [28,29]. Five studies using EUSOMA QIs [22,24-27] were hospital-based and included patients from voluntary centers (often EUSOMA certified centers [22,24-26]), which may introduce selection biases and overestimate compliance. The assessment of health system performance in BC care requires measuring of compliance in “real-life” situations. In 2019, two population-based studies on EUSOMA QIs for the management of BC diagnosed in 2013 and 2016 were conducted in Slovenia and Norway [28,29]. The results of these studies are difficult to generalize to French patients because of differences between health systems. The French system presents some distinguishing features: the importance of private sector which is
<figure><img src="image_6.png" /><figcaption>**Fig 2.** Compliance (%) of each QI by Charlson comorbidity index in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France). The extent of the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum standard for each QI. *p*: Fisher tests were used for QIs 10a/b and 13a/b.</figcaption></figure>

https://doi.org/10.1371/journal.pone.0224275.g002

accessible to all insured patients, complete freedom of provider choice and no limitation of utilization of services.

Regarding pre-operative histological/cytological diagnosis, similar high compliance rates (93–98%) were observed in four recent European studies [20,21,23,29], while two studies that included in situ cancers found lower rates (86–88%) [22,26]. Another French study found perfect compliance, probably due to patient selection (i.e., operable early-stage BC patients managed in CCC, TH and general hospitals) [27]. Older studies found lower compliance rates (60–70%) [10,11,17], except for one study that excluded elderly patients [12].

The guidelines were correctly applied in percentage satisfying the EUSOMA standards for surgical procedures (single operation and BCS for small BC). In most European studies, reexamination rates were similar to ours [10,11,19,25,26], while American studies reported higher rates
<figure><img src="image_6.png" /><figcaption>**Fig 2.** Compliance (%) of each QI by Charlson comorbidity index in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France). The extent of the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum standard for each QI. *p*: Fisher tests were used for QIs 10a/b and 13a/b.</figcaption></figure>

https://doi.org/10.1371/journal.pone.0224275.g002

accessible to all insured patients, complete freedom of provider choice and no limitation of utilization of services.

Regarding pre-operative histological/cytological diagnosis, similar high compliance rates (93–98%) were observed in four recent European studies [20,21,23,29], while two studies that included in situ cancers found lower rates (86–88%) [22,26]. Another French study found perfect compliance, probably due to patient selection (i.e., operable early-stage BC patients managed in CCC, TH and general hospitals) [27]. Older studies found lower compliance rates (60–70%) [10,11,17], except for one study that excluded elderly patients [12].

The guidelines were correctly applied in percentage satisfying the EUSOMA standards for surgical procedures (single operation and BCS for small BC). In most European studies, reexamination rates were similar to ours [10,11,19,25,26], while American studies reported higher rates
<figure><img src="image_7.png" /><figcaption>**Fig 3.** Compliance (%) of each QI by place of first treatment delivery (public and private hospitals, teaching hospital (TH) and comprehensive cancer center (CCC)) in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France). The extent of the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum standard for each QI. *p*: Fisher tests were used for QIs 3b, 8, 10a/b, 11a, 12, 13a/b and 14b.</figcaption></figure>

https://doi.org/10.1371/journal.pone.0224275.g003

(25-40%) [30]. The Norwegian study reported lower reexcision rate (6%) in 2016 [29], in line with the rate decrease observed in another study between 2012 (14.6%) and 2015 (8.8%) [26]. For BCS, variation in compliance was found between studies and may be explained by stage and age differences in the analyzed populations. Compliance rates were similar (81-86%) in European studies that have the same design as ours [22,25,26,29], except for the Slovenian study which reported a low rate (67.5%) [28]. Several American studies reported also low rates (60-70%) in early-stage BCs [31-35]. In our study, 20% of women with small BC underwent mastectomy. In most of them, mastectomy was used to achieve free margins after BCS or was
<figure><img src="image_7.png" /><figcaption>Fig 3. Compliance (%) of each QI by place of first treatment delivery (public and private hospitals, teaching hospital (TH) and comprehensive cancer center (CCC)) in 1 560 patients diagnosed with non-metastatic invasive breast cancers in 2012 (France). The extent of the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum standard for each QI. p: Fisher tests were used for QIs 3b, 8, 10a/b, 11a, 12, 13a/b and 14b.</figcaption></figure>

https://doi.org/10.1371/journal.pone.0224275.g003

(25-40%) [30]. The Norwegian study reported lower reexcision rate (6%) in 2016 [29], in line with the rate decrease observed in another study between 2012 (14.6%) and 2015 (8.8%) [26]. For BCS, variation in compliance was found between studies and may be explained by stage and age differences in the analyzed populations. Compliance rates were similar (81-86%) in European studies that have the same design as ours [22,25,26,29], except for the Slovenian study which reported a low rate (67.5%) [28]. Several American studies reported also low rates (60-70%) in early-stage BCs [31-35]. In our study, 20% of women with small BC underwent mastectomy. In most of them, mastectomy was used to achieve free margins after BCS or was
justified by tumor characteristics. Another primary reason for choosing BCS or mastectomy is patient preference. Radiotherapy was examined after BCS (QI_10a) and after mastectomy for pN≥2a (QI_10b). We reported high compliance (97.8%) for QI_10a. The recent hospital-based European studies found similar rates (94–98%) [22,23,25,26] while lower rates (92–93%) were observed in the Norwegian and Slovenian population-based [28,29]. Older studies found also lower rates [11–13,15,17,20]. In the US, radiotherapy after BCS was less frequent (80%) with geographic disparities [16,34,35]. For QI_10b, the minimum standard (90%) was reached in our study contrary to the two studies reporting low compliance (85.2% in 2008–2012 [25] and 89.9% in 2013 [28]). For these two QIs, non-compliance was mainly due to patient factors in our study.

Regarding hormonotherapy (QI_12a), our results were concordant with previous studies [10,13–15,20,22,23,25,26,28]. Non-compliance was related to patient factors or physician decision based on tumor characteristics (very early-stage, weak hormone receptor-positivity) and the harm/benefit ratio. This is in contradiction with guidelines which recommend hormonotherapy for all endocrine-positive BC, except for small BC (≤T1aN0) [3,36]. Adherence to recommendations for adjuvant chemotherapy (QI_13a) was generally low (83%) but became very high after elderly patients were excluded (96%). This low compliance may also be explained by the preponderance of BC with aggressive phenotypes (triple negative or HER2+) in the eligible population. Neoadjuvant chemotherapy is recommended for these cancers. Two studies reported similar compliances (83–85%) [26,28], while higher rates (90–96%) were seen in the other studies, probably due to exclusion of elderly populations and study design [14,22,24,25]. Compliance with trastuzumab use (QI_13b) was also high in our study. Only the Slovenian study examined this QI and reported a lower rate (87.7%) [28].

The minimum EUSOMA standard was not met for staging practices. For SLNB, low adherence was seen in our study (76%), which is in line with recent European hospital-based studies with similar methods (81–82%) [24,25]. Like an American hospital-based study finding a higher compliance rate (87%) in 2009 [18], a higher compliance rate (89.5%) was observed in Slovenia in 2013 [28], probably due to the fact that BC management is centralized. ALND was chosen in place of SLNB in 17.5% of eligible women, whereas the others did not have surgery. SLNB is indicated for staging patients with early BC (T1-T2N0) [3,37]. In France, this recommendation is restricted to T1-T2 (≤30mm) BC [36]. When tumor size (≤30mm) was considered, compliance remained low at 81.0%. Thus, this low adherence mainly indicates a possible aggressive treatment approach, even if some prognostic factors (such as multifocality/multicentricity, high grade, and triple negativity) may have influenced the choice of this approach. Besides SLNB helps to choose the best treatment for each patient, it reduces the chance of related arm morbidity, common after ALND. Moreover, guidelines were not followed for metastatic work-up: imaging was performed too often in early BC (stages I-II) and not enough often in stage III BC. These observations have already been reported in several studies [17,38,39]. Guidelines recommend imaging only for patients with symptomatic early BC and stage III BC because the reported probability of occult distant metastasis in stage I-II BC is exceedingly low (0.3–1.2%) [3,4,38]. In our study, we could not distinguish between asymptomatic and symptomatic BC, which might limit our interpretations. However, non-compliance was very high and could not entirely be explained by symptomatic women. Non-compliance could be explained by patient- and physician-related factors [40,41]. Physician behavior in ordering unnecessary tests might be partly driven by patient demand [40]. Fear of malpractice litigation may be another explanation. Given the cost and morbidity associated with unnecessary tests, patient and physician education regarding performing appropriate tests is required.
justified by tumor characteristics. Another primary reason for choosing BCS or mastectomy is patient preference. Radiotherapy was examined after BCS (QI_10a) and after mastectomy for pN≥2a (QI_10b). We reported high compliance (97.8%) for QI_10a. The recent hospital-based European studies found similar rates (94–98%) [22,23,25,26] while lower rates (92–93%) were observed in the Norwegian and Slovenian population-based [28,29]. Older studies found also lower rates [11–13,15,17,20]. In the US, radiotherapy after BCS was less frequent (80%) with geographic disparities [16,34,35]. For QI_10b, the minimum standard (90%) was reached in our study contrary to the two studies reporting low compliance (85.2% in 2008–2012 [25] and 89.9% in 2013 [28]). For these two QIs, non-compliance was mainly due to patient factors in our study.

Regarding hormonotherapy (QI_12a), our results were concordant with previous studies [10,13–15,20,22,23,25,26,28]. Non-compliance was related to patient factors or physician decision based on tumor characteristics (very early-stage, weak hormone receptor-positivity) and the harm/benefit ratio. This is in contradiction with guidelines which recommend hormonotherapy for all endocrine-positive BC, except for small BC (≤T1aN0) [3,36]. Adherence to recommendations for adjuvant chemotherapy (QI_13a) was generally low (83%) but became very high after elderly patients were excluded (96%). This low compliance may also be explained by the preponderance of BC with aggressive phenotypes (triple negative or HER2+) in the eligible population. Neoadjuvant chemotherapy is recommended for these cancers. Two studies reported similar compliances (83–85%) [26,28], while higher rates (90–96%) were seen in the other studies, probably due to exclusion of elderly populations and study design [14,22,24,25]. Compliance with trastuzumab use (QI_13b) was also high in our study. Only the Slovenian study examined this QI and reported a lower rate (87.7%) [28].

The minimum EUSOMA standard was not met for staging practices. For SLNB, low adherence was seen in our study (76%), which is in line with recent European hospital-based studies with similar methods (81–82%) [24,25]. Like an American hospital-based study finding a higher compliance rate (87%) in 2009 [18], a higher compliance rate (89.5%) was observed in Slovenia in 2013 [28], probably due to the fact that BC management is centralized. ALND was chosen in place of SLNB in 17.5% of eligible women, whereas the others did not have surgery. SLNB is indicated for staging patients with early BC (T1-T2N0) [3,37]. In France, this recommendation is restricted to T1-T2 (≤30mm) BC [36]. When tumor size (≤30mm) was considered, compliance remained low at 81.0%. Thus, this low adherence mainly indicates a possible aggressive treatment approach, even if some prognostic factors (such as multifocality/multicentricity, high grade, and triple negativity) may have influenced the choice of this approach. Besides SLNB helps to choose the best treatment for each patient, it reduces the chance of related arm morbidity, common after ALND. Moreover, guidelines were not followed for metastatic work-up: imaging was performed too often in early BC (stages I-II) and not enough often in stage III BC. These observations have already been reported in several studies [17,38,39]. Guidelines recommend imaging only for patients with symptomatic early BC and stage III BC because the reported probability of occult distant metastasis in stage I-II BC is exceedingly low (0.3–1.2%) [3,4,38]. In our study, we could not distinguish between asymptomatic and symptomatic BC, which might limit our interpretations. However, non-compliance was very high and could not entirely be explained by symptomatic women. Non-compliance could be explained by patient- and physician-related factors [40,41]. Physician behavior in ordering unnecessary tests might be partly driven by patient demand [40]. Fear of malpractice litigation may be another explanation. Given the cost and morbidity associated with unnecessary tests, patient and physician education regarding performing appropriate tests is required.
Finally, we found high adherence for MTM. The other French study also observed high
compliance (94–95%), except for TH (32%) [27]. Although MTM has become standard in BC
management in many countries worldwide, few studies have examined how many patients
benefit from it. Stordeur et al. found an 80.3% compliance rate in 2006 [11]. Kowalsky et al.
found rates from 58.3% (pre-treatment MTM) to 100% (post-operative MTM) in 2012 [23]. In
our study, MTM was positively related to high-quality care in line with guidelines, especially
the confirmation of the malignant diagnosis—which is required for ascertaining the optimal
treatment -, the choice of the appropriate systemic treatments and SNLB use, a more recent
staging practice.

Elderly patients were less likely to receive care that conformed to guidelines, which was
consistent with previous studies [16,17,25,42]. These results may reflect undertreatment but
can be related to patient preferences [43]. However, strong evidence exists that more conserva-
tive approaches to surgery and post-operative radiotherapy may be adopted in older patients
without affecting survival [44–46]. Similarly, systemic therapies should be adapted to health
status and harm/benefit ratio. This result may partly explain why EUSOMA has recently pro-
posed the exclusion of older patients when adherence fails to meet the minimum standard for
some QIs [4]. The same conclusions can be drawn regarding lower compliance in patients
with comorbidities, who are often elderly [17,42,47]. Variation in treatment compliance
between type of heath care facilities has already been reported [17,27,48]. It may be related not
only to patient and tumor characteristics (age, stage) but also to hospital and physician charac-
teristics. Indeed, surgical procedures can vary with the medical practices of each physician,
team habits or organizational factors. Territorial differences partly reflect differences in health
care provisions between departments (i.e., variation in screening, distribution of hospital cate-
gories, access to some treatments such radiotherapy, and coordination care). They may also be
explained by patient characteristics and physician preferences. However, minimum adherence
levels should be met regardless of patient recruitment or the geographical location of health
care organizations.

The main strengths of this study include its population-based design, which allowed assess-
ment of quality care without selection bias, and data quality (few missing data). The sample
procedure ensures that our sample is representative of a large population of BC patients and
allows to describe the heterogeneity of medical practices in France.

However, the small number of cases for certain QIs may limit interpretations. Quality care
analysis requires assessments of reasons for non-compliance because guideline may not be
applied for every patient. We evaluated these reasons for most QI, except for BCS and trastuzu-
mab. Following EUSOMA [4], our study analyzed non-metastatic BC. Complementary analy-
ses including all invasive BC showed similar results.

Conclusions

Our study provides the first current, comprehensive overview of BC quality care in France at a
population-level. The guidelines were correctly applied in percentage satisfying the EUSOMA
standards for the diagnosis and treatment of non-metastatic BC, although staging practices
(SLNB, imaging) can be improved. Measurement of indicators is the starting point for under-
standing how to improve practices. This study may contribute to updating guidelines and can
be used as baseline information prior to assessing the current national Cancer Plan.

**Supporting information**

S1 Fig. Compliance (%) of each QI by geographical area of residence covered by registries
in 1 560 non-metastatic invasive breast cancers diagnosed in 2012 (France). The extent of
Finally, we found high adherence for MTM. The other French study also observed high
compliance (94–95%), except for TH (32%) [27]. Although MTM has become standard in BC
management in many countries worldwide, few studies have examined how many patients
benefit from it. Stordeur et al. found an 80.3% compliance rate in 2006 [11]. Kowalsky et al.
found rates from 58.3% (pre-treatment MTM) to 100% (post-operative MTM) in 2012 [23]. In
our study, MTM was positively related to high-quality care in line with guidelines, especially
the confirmation of the malignant diagnosis—which is required for ascertaining the optimal
treatment -, the choice of the appropriate systemic treatments and SNLB use, a more recent
staging practice.

Elderly patients were less likely to receive care that conformed to guidelines, which was
consistent with previous studies [16,17,25,42]. These results may reflect undertreatment but
can be related to patient preferences [43]. However, strong evidence exists that more conserva-
tive approaches to surgery and post-operative radiotherapy may be adopted in older patients
without affecting survival [44–46]. Similarly, systemic therapies should be adapted to health
status and harm/benefit ratio. This result may partly explain why EUSOMA has recently pro-
posed the exclusion of older patients when adherence fails to meet the minimum standard for
some QIs [4]. The same conclusions can be drawn regarding lower compliance in patients
with comorbidities, who are often elderly [17,42,47]. Variation in treatment compliance
between type of heath care facilities has already been reported [17,27,48]. It may be related not
only to patient and tumor characteristics (age, stage) but also to hospital and physician charac-
teristics. Indeed, surgical procedures can vary with the medical practices of each physician,
team habits or organizational factors. Territorial differences partly reflect differences in health
care provisions between departments (i.e., variation in screening, distribution of hospital cate-
gories, access to some treatments such radiotherapy, and coordination care). They may also be
explained by patient characteristics and physician preferences. However, minimum adherence
levels should be met regardless of patient recruitment or the geographical location of health
care organizations.

The main strengths of this study include its population-based design, which allowed assess-
ment of quality care without selection bias, and data quality (few missing data). The sample
procedure ensures that our sample is representative of a large population of BC patients and
allows to describe the heterogeneity of medical practices in France.

However, the small number of cases for certain QIs may limit interpretations. Quality care
analysis requires assessments of reasons for non-compliance because guideline may not be
applied for every patient. We evaluated these reasons for most QI, except for BCS and trastuzu-
mab. Following EUSOMA [4], our study analyzed non-metastatic BC. Complementary analy-
ses including all invasive BC showed similar results.

Conclusions

Our study provides the first current, comprehensive overview of BC quality care in France at a
population-level. The guidelines were correctly applied in percentage satisfying the EUSOMA
standards for the diagnosis and treatment of non-metastatic BC, although staging practices
(SLNB, imaging) can be improved. Measurement of indicators is the starting point for under-
standing how to improve practices. This study may contribute to updating guidelines and can
be used as baseline information prior to assessing the current national Cancer Plan.

**Supporting information**

S1 Fig. Compliance (%) of each QI by geographical area of residence covered by registries
in 1 560 non-metastatic invasive breast cancers diagnosed in 2012 (France). The extent of
the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum
standard for each QI. The geographical areas are represented by official area codes. Compli-
ance range is defined as the difference between the maximum and minimum compliances for
each QI. p: Fisher tests were used for all QIs except QI_11c.
(TIF)

**Acknowledgments**

The authors thank all data sources that contributed to cancer registration by registries, particu-
larly pathologists, medical information departments at public and private hospitals, medical
departments of health insurance organizations, and general practitioners and specialists. They
also thank Milena Sant (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) for
revising this manuscript.

Cancer registries are supported by the French National Cancer Institute (INCa), Santé Pub-
lique France, Direction Générale de l'Offre de Soins (DGOS), local institutions and League
Against Cancer.

**Members of the FRANCIM group:**

Gaëlle Coureau (Gironde Cancer Registry),
Patrick Arveux (Côte d'Or Breast Cancer Registry),
Simona Bara (Manche Cancer Registry),
Patricia Delafosse (Isère Cancer Registry),
Laetitia Daubisse-Marliac, Pascale Grosclaude (Tarn Cancer Registry),
Gautier Defossez (Poitou-Charentes Cancer Registry),
Anne-Valérie Guizard (Calvados General Tumor Registry),
Karine Jéhannin-Ligier (General Cancer Registry of Lille and its area),
Bénédicte Lapôtre-Ledoux (Somme Cancer Registry),
Nathalie Leone (Haute Vienne Cancer Registry),
Emilie Marrer (Haut-Rhin Cancer Registry),
Brigitte Trétarre (Hérault Cancer Registry),
Michel Velten (Bas-Rhin Cancer Registry),
Anne-Sophie Woronoff (Doubs and Belfort Territory Cancer Registry),
Anne Cowppli-Bony, Florence Molinié (Loire-Atlantique Vendee Cancer Registry).

**Author Contributions**

**Conceptualization:** Anne Cowppli-Bony, Brigitte Trétarre, Florence Molinié.

**Data curation:** Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laeti-
tia Daubisse-Marliac, Gaelle Coureau, Anne-Sophie Woronoff, Patricia Delafosse, Florence
Molinié.

**Formal analysis:** Anne Cowppli-Bony, Pamela Minicozzi, Florence Molinié.

**Investigation:** Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laeti-
tia Daubisse-Marliac, Gaelle Coureau, Anne-Sophie Woronoff, Patricia Delafosse, Florence
Molinié.

**Methodology:** Anne Cowppli-Bony, Pamela Minicozzi, Florence Molinié.

**Project administration:** Florence Molinié.

**Supervision:** Florence Molinié.
the Y scale for compliance (%) is different across QIs. The dotted line represents the minimum standard for each QI. The geographical areas are represented by official area codes. Compliance range is defined as the difference between the maximum and minimum compliances for each QI. p: Fisher tests were used for all QIs except QI_11c.

(TIF)

**Acknowledgments**

The authors thank all data sources that contributed to cancer registration by registries, particularly pathologists, medical information departments at public and private hospitals, medical departments of health insurance organizations, and general practitioners and specialists. They also thank Milena Sant (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) for revising this manuscript.

Cancer registries are supported by the French National Cancer Institute (INCa), Santé Publique France, Direction Générale de l'Offre de Soins (DGOS), local institutions and League Against Cancer.

**Members of the FRANCIM group:**

Gaëlle Coureau (Gironde Cancer Registry),
Patrick Arveux (Côte d'Or Breast Cancer Registry),
Simona Bara (Manche Cancer Registry),
Patricia Delafosse (Isère Cancer Registry),
Laetitia Daubisse-Marliac, Pascale Grosclaude (Tarn Cancer Registry),
Gautier Defossez (Poitou-Charentes Cancer Registry),
Anne-Valérie Guizard (Calvados General Tumor Registry),
Karine Jéhannin-Ligier (General Cancer Registry of Lille and its area),
Bénédicte Lapôtre-Ledoux (Somme Cancer Registry),
Nathalie Leone (Haute Vienne Cancer Registry),
Emilie Marrer (Haut-Rhin Cancer Registry),
Brigitte Trétarre (Hérault Cancer Registry),
Michel Velten (Bas-Rhin Cancer Registry),
Anne-Sophie Woronoff (Doubs and Belfort Territory Cancer Registry),
Anne Cowppli-Bony, Florence Molinié (Loire-Atlantique Vendee Cancer Registry).

**Author Contributions**

**Conceptualization:** Anne Cowppli-Bony, Brigitte Trétarre, Florence Molinié.

**Data curation:** Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, Gaelle Coureau, Anne-Sophie Woronoff, Patricia Delafosse, Florence Molinié.

**Formal analysis:** Anne Cowppli-Bony, Pamela Minicozzi, Florence Molinié.

**Investigation:** Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, Gaelle Coureau, Anne-Sophie Woronoff, Patricia Delafosse, Florence Molinié.

**Methodology:** Anne Cowppli-Bony, Pamela Minicozzi, Florence Molinié.

**Project administration:** Florence Molinié.

**Supervision:** Florence Molinié.
**Validation:** Anne Cowppli-Bony.

**Writing – original draft:** Anne Cowppli-Bony, Florence Molinié.

**Writing – review & editing:** Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, Gaelle Coureau, Pamela Minicozzi, Anne-Sophie Woronoff, Patricia Delafosse, Florence Molinié.

## References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394–424. https://doi.org/10.3322/caac.21492 PMID: 30207593

2. Defossez G, Le Guyader-Peyrou S, Uhry Z, Grosclaude P, Colonna M, Dantony E, et al. Cancer incidence and mortality in France over the 1990–2018 period: solid tumors. Saint-Maurice: Santé publique France; 2019. https://www.e-cancer.fr/

3. Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 Suppl 5:v8–30.

4. Biganzoli L, Marotti L, Hart CD, Cataliotti L, Cutuli B, Kühn T, et al. Quality indicators in breast cancer care: An update from the EUSOMA working group. Eur J Cancer. 2017; 86:59–81. https://doi.org/10.1016/j.ejca.2017.08.017 PMID: 28963914

5. Desch CE, McNiff KK, Schneider EC, Schrag D, McClure J, Lepisto E, et al. American Society of Clinical Oncology/National Comprehensive Cancer Network Quality Measures. J Clin Oncol. 2008; 26 (21):3631–7. https://doi.org/10.1200/JCO.2008.16.5068 PMID: 18640941

6. Schnitt SJ. Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy. Mod Pathol. 2010; 23 Suppl 2:S60–64.

7. Del Turco MR, Ponti A, Bick U, Biganzoli L, Cserni G, Cutuli B, et al. Quality indicators in breast cancer care. Eur J Cancer. 2010; 46(13):2344–56. https://doi.org/10.1016/j.ejca.2010.06.119 PMID: 20675120

8. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373–83. https://doi.org/10.1016/0021-9681(87)90171-8 PMID: 3558716

9. Minicozzi P, Cirilli C, Federico M, Capocaccia R, Budroni M, Candela P, et al. Differences in stage and treatment of breast cancer across Italy point to inequalities in access to and availability of proper care. Tumori. 2012; 98(2):204–9. https://doi.org/10.1700/1088.11930 PMID: 22677985

10. Sacerdote C, Bordon R, Pitarella S, Mano MP, Baldi I, Casella D, et al. Compliance with clinical practice guidelines for breast cancer treatment: a population-based study of quality-of-care indicators in Italy. BMC Health Serv Res. 2013; 13:28. https://doi.org/10.1186/1472-6963-13-28 PMID: 23351327

11. Stordeur S, Vrijens F, Devriese S, Beirens K, Van Eycken E, Vlayen J. Developing and measuring a set of process and outcome indicators for breast cancer. Breast. 2012; 21(3):253–60. https://doi.org/10.1016/j.breast.2011.10.003 PMID: 22056787

12. Caldarella A, Amunni G, Angiolini C, Crocetti E, Di Costanzo F, Di Leo A, et al. Feasibility of evaluating quality cancer care using registry data and electronic health records: a population-based study. Int J Qual Health Care. 2012; 24(4):411–8. https://doi.org/10.1093/intqhc/mzs020 PMID: 22597705

13. Barni S, Venturini M, Molino A, Donadio M, Rizzoli S, Maiello E, et al. Importance of adherence to guidelines in breast cancer clinical practice. The Italian experience (AIOM). Tumori. 2011; 97(5):559–63. https://doi.org/10.1700/989.10711 PMID: 22158483

14. Jacobson JO, Neuss MN, McNiff KK, Kadlubek P, Thacker LR, Song F, et al. Improvement in oncology practice performance through voluntary participation in the Quality Oncology Practice Initiative. J Clin Oncol. 2008; 26(11):1893–8. https://doi.org/10.1200/JCO.2007.14.2992 PMID: 18398155

15. Brucker SY, Schumacher C, Sohn C, Rezai M, Bamberg M, Wallwiener D. Benchmarking the quality of breast cancer care in a nationwide voluntary system: the first five-year results (2003–2007) from Germany as a proof of concept. BMC Cancer. 2008; 8:358. https://doi.org/10.1186/1471-2407-8-358 PMID: 19055735

16. Dean CT, Jubelirer SJ, Plants BA, Welch CA. Use of radiation after breast conserving surgery (BCS) for DCIS and early invasive breast cancer at Charleston Area Medical Center (CAMC). A study of compliance with National Comprehensive Cancer Network (NCCN) guidelines. W V Med J. 2009; 105 Spec No:34–8; quiz 39.
**Validation:** Anne Cowppli-Bony.

**Writing – original draft:** Anne Cowppli-Bony, Florence Molinié.

**Writing – review & editing:** Anne Cowppli-Bony, Brigitte Trétarre, Emilie Marrer, Gautier Defossez, Laetitia Daubisse-Marliac, Gaelle Coureau, Pamela Minicozzi, Anne-Sophie Woronoff, Patricia Delafosse, Florence Molinié.

## References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394–424. https://doi.org/10.3322/caac.21492 PMID: 30207593

2. Defossez G, Le Guyader-Peyrou S, Uhry Z, Grosclaude P, Colonna M, Dantony E, et al. Cancer incidence and mortality in France over the 1990–2018 period: solid tumors. Saint-Maurice: Santé publique France; 2019. https://www.e-cancer.fr/

3. Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 Suppl 5:v8–30.

4. Biganzoli L, Marotti L, Hart CD, Cataliotti L, Cutuli B, Kühn T, et al. Quality indicators in breast cancer care: An update from the EUSOMA working group. Eur J Cancer. 2017; 86:59–81. https://doi.org/10.1016/j.ejca.2017.08.017 PMID: 28963914

5. Desch CE, McNiff KK, Schneider EC, Schrag D, McClure J, Lepisto E, et al. American Society of Clinical Oncology/National Comprehensive Cancer Network Quality Measures. J Clin Oncol. 2008; 26 (21):3631–7. https://doi.org/10.1200/JCO.2008.16.5068 PMID: 18640941

6. Schnitt SJ. Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy. Mod Pathol. 2010; 23 Suppl 2:S60–64.

7. Del Turco MR, Ponti A, Bick U, Biganzoli L, Cserni G, Cutuli B, et al. Quality indicators in breast cancer care. Eur J Cancer. 2010; 46(13):2344–56. https://doi.org/10.1016/j.ejca.2010.06.119 PMID: 20675120

8. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373–83. https://doi.org/10.1016/0021-9681(87)90171-8 PMID: 3558716

9. Minicozzi P, Cirilli C, Federico M, Capocaccia R, Budroni M, Candela P, et al. Differences in stage and treatment of breast cancer across Italy point to inequalities in access to and availability of proper care. Tumori. 2012; 98(2):204–9. https://doi.org/10.1700/1088.11930 PMID: 22677985

10. Sacerdote C, Bordon R, Pitarella S, Mano MP, Baldi I, Casella D, et al. Compliance with clinical practice guidelines for breast cancer treatment: a population-based study of quality-of-care indicators in Italy. BMC Health Serv Res. 2013; 13:28. https://doi.org/10.1186/1472-6963-13-28 PMID: 23351327

11. Stordeur S, Vrijens F, Devriese S, Beirens K, Van Eycken E, Vlayen J. Developing and measuring a set of process and outcome indicators for breast cancer. Breast. 2012; 21(3):253–60. https://doi.org/10.1016/j.breast.2011.10.003 PMID: 22056787

12. Caldarella A, Amunni G, Angiolini C, Crocetti E, Di Costanzo F, Di Leo A, et al. Feasibility of evaluating quality cancer care using registry data and electronic health records: a population-based study. Int J Qual Health Care. 2012; 24(4):411–8. https://doi.org/10.1093/intqhc/mzs020 PMID: 22597705

13. Barni S, Venturini M, Molino A, Donadio M, Rizzoli S, Maiello E, et al. Importance of adherence to guidelines in breast cancer clinical practice. The Italian experience (AIOM). Tumori. 2011; 97(5):559–63. https://doi.org/10.1700/989.10711 PMID: 22158483

14. Jacobson JO, Neuss MN, McNiff KK, Kadlubek P, Thacker LR, Song F, et al. Improvement in oncology practice performance through voluntary participation in the Quality Oncology Practice Initiative. J Clin Oncol. 2008; 26(11):1893–8. https://doi.org/10.1200/JCO.2007.14.2992 PMID: 18398155

15. Brucker SY, Schumacher C, Sohn C, Rezai M, Bamberg M, Wallwiener D. Benchmarking the quality of breast cancer care in a nationwide voluntary system: the first five-year results (2003–2007) from Germany as a proof of concept. BMC Cancer. 2008; 8:358. https://doi.org/10.1186/1471-2407-8-358 PMID: 19055735

16. Dean CT, Jubelirer SJ, Plants BA, Welch CA. Use of radiation after breast conserving surgery (BCS) for DCIS and early invasive breast cancer at Charleston Area Medical Center (CAMC). A study of compliance with National Comprehensive Cancer Network (NCCN) guidelines. W V Med J. 2009; 105 Spec No:34–8; quiz 39.
17. Andreano A, Anghinoni E, Autelitano M, Bellini A, Bersani M, Bizzoco S, et al. Indicators based on registers and administrative data for breast cancer: routine evaluation of oncologic care pathway can be implemented. J Eval Clin Pract. 2016; 22(1):62-70. https://doi.org/10.1111/jep.12436 PMID: 26290172

18. Laronga C, Gray JE, Siegel EM, Lee J-H, Fulp WJ, Fletcher M, et al. Florida Initiative for Quality Cancer Care: Improvements in Breast Cancer Quality Indicators During a 3-Year Interval. J Am Coll Surg. 2014; 219(4):638-45.e1. https://doi.org/10.1016/j.jamcollsurg.2014.03.063 PMID: 25086813

19. van Hoeve J, de Munck L, Otter R, de Vries J, Siesling S. Quality improvement by implementing an integrated oncological care pathway for breast cancer patients. Breast. 2014; 23(4):364-70. https://doi.org/10.1016/j.breast.2014.01.008 PMID: 24582455

20. Wallwiener M, Brucker SY, Wallwiener D, Steering Committee. Multidisciplinary breast centres in Germany: a review and update of quality assurance through benchmarking and certification. Arch Gynecol Obstet. 2012; 285(6):1671-83. https://doi.org/10.1007/s00404-011-2212-3 PMID: 22314433

21. Garcia-Etienne CA, Tomatis M, Heil J, Friedrichs K, Kreienberg R, Denk A, et al. Mastectomy trends for early-stage breast cancer: A report from the EUSOMA multi-institutional European database. Eur J Cancer. 2012; 48(13):1947-56. https://doi.org/10.1016/j.ejca.2012.03.008 PMID: 22483323

22. van Dam PA, Verheyden G, Sugihara A, Trinh XB, Van Der Mussele H, Wuyts H, et al. A dynamic clinical pathway for the treatment of patients with early breast cancer is a tool for better cancer care: implementation and prospective analysis between 2002-2010. World J Surg Oncol. 2013; 11:70. https://doi.org/10.1186/1477-7819-11-70 PMID: 23497270

23. Kowalski C, Ferencz J, Brucker SY, Kreienberg R, Wesselmann S. Quality of care in breast cancer centers: Results of benchmarking by the German Cancer Society and German Society for Breast Diseases. Breast. 2015; 24(2):118-23. https://doi.org/10.1016/j.breast.2014.11.014 PMID: 25515645

24. van Dam PA, Tomatis M, Marotti L, Heil J, Wilson R, Rosselli Del Turco M, et al. The effect of EUSOMA certification on quality of breast cancer care. Eur J Surg Oncol. 2015; 41(10):1423-9. https://doi.org/10.1016/j.ejso.2015.06.006 PMID: 26278019

25. Kiderlen M, Ponti A, Tomatis M, Boelens PG, Bastiaannet E, Wilson R, et al. Variations in compliance to quality indicators by age for 41,871 breast cancer patients across Europe: A European Society of Breast Cancer Specialists database analysis. Eur J Cancer. 2015; 51(10):1221-30. https://doi.org/10.1016/j.ejca.2015.03.013 PMID: 25892645

26. van Dam PA, Tomatis M, Marotti L, Heil J, Mansel RE, Rosselli del Turco M, et al. Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres. Eur J Cancer. 2017; 85(Supplement C):15-22.

27. Héquet D, Huchon C, Baffert S, Alran S, Reyal F, Nguyen T, et al. Preoperative clinical pathway of breast cancer patients: determinants of compliance with EUSOMA quality indicators. Br J Cancer. 2017; 116(11):1394-1401. https://doi.org/10.1038/bjc.2017.114 PMID: 28441385

28. Plavc G, Ratoša I, Žagar T, Zadnik V. Explaining variation in quality of breast cancer care and its impact: a nationwide population-based study from Slovenia. Breast Cancer Res Treat. 2019; 175(3):585-94. https://doi.org/10.1007/s10549-019-05186-z PMID: 30847727

29. Hartmann-Johnsen OJ, Kâresen R, Schlichting E, Naume B, Nygård JF. Using clinical cancer registry data for estimation of quality indicators: Results from the Norwegian breast cancer registry. Int J Med Inf. 2019; 125:102-9.

30. Wilke LG, Czechura T, Wang C, Lapin B, Liederbach E, Winchester DP, et al. Repeat Surgery After Breast Conservation for the Treatment of Stage 0 to II Breast Carcinoma: A Report From the National Cancer Data Base, 2004-2010. JAMA Surg. 2014; 149(12):1296-305. https://doi.org/10.1001/jamasurg.2014.926 PMID: 25390819

31. Churilla TM, Donnelly PE, Leatherman ER, Adonizio CS, Peters CA. Total Mastectomy or Breast Conservation Therapy? How Radiation Oncologist Accessibility Determines Treatment Choice and Quality: A SEER Data-base Analysis. Breast J. 2015; 21(5):473-80. https://doi.org/10.1111/tbj.12449 PMID: 26133235

32. Daroui P, Gabel M, Khan AJ, Haffty BG, Goyal S. Utilization of breast conserving therapy in stages 0, I, and II breast cancer patients in New Jersey: an American College of Surgeons National Cancer Data Base (NCDB) analysis. Am J Clin Oncol. 2012; 35(2):130-5. https://doi.org/10.1097/COC. 0b013e318209aa57 PMID: 21325935

33. Patrick JL, Hasse ME, Feinglass J, Khan SA. Trends in adherence to NCCN guidelines for breast conserving therapy in women with Stage I and II breast cancer: Analysis of the 1998-2008 National Cancer Data Base. Surg Oncol. 2017; 26(4):359-67. https://doi.org/10.1016/j.suronc.2017.07.006 PMID: 29113653

34. Showalter SL, Grover S, Sharma S, Lin L, Czerniecki BJ. Factors Influencing Surgical and Adjuvant Therapy in Stage I Breast Cancer: A SEER 18 Database Analysis. Ann Surg Oncol. 2013; 20(4):1287-94. https://doi.org/10.1245/s10434-012-2693-8 PMID: 23135311
17. Andreano A, Anghinoni E, Autelitano M, Bellini A, Bersani M, Bizzoco S, et al. Indicators based on registers and administrative data for breast cancer: routine evaluation of oncologic care pathway can be implemented. J Eval Clin Pract. 2016; 22(1):62–70. https://doi.org/10.1111/jep.12436 PMID: 26290172

18. Laronga C, Gray JE, Siegel EM, Lee J-H, Fulp WJ, Fletcher M, et al. Florida Initiative for Quality Cancer Care: Improvements in Breast Cancer Quality Indicators During a 3-Year Interval. J Am Coll Surg. 2014; 219(4):638–45.e1. https://doi.org/10.1016/j.jamcollsurg.2014.03.063 PMID: 25086813

19. van Hoeve J, de Munck L, Otter R, de Vries J, Siesling S. Quality improvement by implementing an integrated oncological care pathway for breast cancer patients. Breast. 2014; 23(4):364–70. https://doi.org/10.1016/j.breast.2014.01.008 PMID: 24582455

20. Wallwiener M, Brucker SY, Wallwiener D, Steering Committee. Multidisciplinary breast centres in Germany: a review and update of quality assurance through benchmarking and certification. Arch Gynecol Obstet. 2012; 285(6):1671–83. https://doi.org/10.1007/s00404-011-2212-3 PMID: 22314433

21. Garcia-Etienne CA, Tomatis M, Heil J, Friedrichs K, Kreienberg R, Denk A, et al. Mastectomy trends for early-stage breast cancer: A report from the EUSOMA multi-institutional European database. Eur J Cancer. 2012; 48(13):1947–56. https://doi.org/10.1016/j.ejca.2012.03.008 PMID: 22483323

22. van Dam PA, Verheyden G, Sugihara A, Trinh XB, Van Der Mussele H, Wuyts H, et al. A dynamic clinical pathway for the treatment of patients with early breast cancer is a tool for better cancer care: implementation and prospective analysis between 2002–2010. World J Surg Oncol. 2013; 11:70. https://doi.org/10.1186/1477-7819-11-70 PMID: 23497270

23. Kowalski C, Ferencz J, Brucker SY, Kreienberg R, Wesselmann S. Quality of care in breast cancer centers: Results of benchmarking by the German Cancer Society and German Society for Breast Diseases. Breast. 2015; 24(2):118–23. https://doi.org/10.1016/j.breast.2014.11.014 PMID: 25515645

24. van Dam PA, Tomatis M, Marotti L, Heil J, Wilson R, Rosselli Del Turco M, et al. The effect of EUSOMA certification on quality of breast cancer care. Eur J Surg Oncol. 2015; 41(10):1423–9. https://doi.org/10.1016/j.ejso.2015.06.006 PMID: 26278019

25. Kiderlen M, Ponti A, Tomatis M, Boelens PG, Bastiaannet E, Wilson R, et al. Variations in compliance to quality indicators by age for 41,871 breast cancer patients across Europe: A European Society of Breast Cancer Specialists database analysis. Eur J Cancer. 2015; 51(10):1221–30. https://doi.org/10.1016/j.ejca.2015.03.013 PMID: 25892645

26. van Dam PA, Tomatis M, Marotti L, Heil J, Mansel RE, Rosselli del Turco M, et al. Time trends (2006–2015) of quality indicators in EUSOMA-certified breast centres. Eur J Cancer. 2017; 85(Supplement C):15–22.

27. Héquet D, Huchon C, Baffert S, Alran S, Reyal F, Nguyen T, et al. Preoperative clinical pathway of breast cancer patients: determinants of compliance with EUSOMA quality indicators. Br J Cancer. 2017; 116(11):1394–1401. https://doi.org/10.1038/bjc.2017.114 PMID: 28441385

28. Plavc G, Ratoša I, Žagar T, Zadnik V. Explaining variation in quality of breast cancer care and its impact: a nationwide population-based study from Slovenia. Breast Cancer Res Treat. 2019; 175(3):585–94. https://doi.org/10.1007/s10549-019-05186-z PMID: 30847727

29. Hartmann-Johnsen OJ, Kâresen R, Schlichting E, Naume B, Nygård JF. Using clinical cancer registry data for estimation of quality indicators: Results from the Norwegian breast cancer registry. Int J Med Inf. 2019; 125:102–9.

30. Wilke LG, Czechura T, Wang C, Lapin B, Liederbach E, Winchester DP, et al. Repeat Surgery After Breast Conservation for the Treatment of Stage 0 to II Breast Carcinoma: A Report From the National Cancer Data Base, 2004–2010. JAMA Surg. 2014; 149(12):1296–305. https://doi.org/10.1001/jamasurg.2014.926 PMID: 25390819

31. Churilla TM, Donnelly PE, Leatherman ER, Adonizio CS, Peters CA. Total Mastectomy or Breast Conservation Therapy? How Radiation Oncologist Accessibility Determines Treatment Choice and Quality: A SEER Data-base Analysis. Breast J. 2015; 21(5):473–80. https://doi.org/10.1111/tbj.12449 PMID: 26133235

32. Daroui P, Gabel M, Khan AJ, Haffty BG, Goyal S. Utilization of breast conserving therapy in stages 0, I, and II breast cancer patients in New Jersey: an American College of Surgeons National Cancer Data Base (NCDB) analysis. Am J Clin Oncol. 2012; 35(2):130–5. https://doi.org/10.1097/COC. 0b013e318209aa57 PMID: 21325935

33. Patrick JL, Hasse ME, Feinglass J, Khan SA. Trends in adherence to NCCN guidelines for breast conserving therapy in women with Stage I and II breast cancer: Analysis of the 1998–2008 National Cancer Data Base. Surg Oncol. 2017; 26(4):359–67. https://doi.org/10.1016/j.suronc.2017.07.006 PMID: 29113653

34. Showalter SL, Grover S, Sharma S, Lin L, Czerniecki BJ. Factors Influencing Surgical and Adjuvant Therapy in Stage I Breast Cancer: A SEER 18 Database Analysis. Ann Surg Oncol. 2013; 20(4):1287–94. https://doi.org/10.1245/s10434-012-2693-8 PMID: 23135311
35. Fisher S, Gao H, Yasui Y, Dabbs K, Winget M. Treatment variation in patients diagnosed with early stage breast cancer in Alberta from 2002 to 2010: a population-based study. BMC Health Serv Res. 2015; 15:35. https://doi.org/10.1186/s12913-015-0680-z PMID: 25609420

36. Gligorov J, Krakowski I, Luporsi E, Namer M. [Recommandations pour la Pratique Clinique : Nice—Saint-Paul-de-Vence 2011 / « Cancers du sein : recommandations et veille bibliographique »]. Oncologie. 2011; 13(10–11).

37. Chatterjee A, Serniak N, Czerniecki BJ. Sentinel Lymph Node Biopsy in Breast Cancer: A Work in Progress. Cancer J. 2015; 21(1):7–10. https://doi.org/10.1097/PPO.0000000000000090 PMID: 25611773

38. Chagpar A, Babiera G, Aguirre J, Caropreso P, Hughes T, American College of Surgeons Communities. Variation in metastatic workup for patients with invasive breast cancer. Am J Surg. 2015; 210(6):1147–1154.e2; discussion 1153–1154. https://doi.org/10.1016/j.amjsurg.2015.06.032 PMID: 26518161

39. Simos D, Catley C, van Walraven C, Arnaout A, Booth CM, McInnes M, et al. Imaging for distant metastases in women with early-stage breast cancer: a population-based cohort study. Can Med Assoc J. 2015; 187(12):E387–97.

40. Simos D, Hutton B, Graham ID, Arnaout A, Caudrelier J-M, Mazzarello S, et al. Patient perceptions and expectations regarding imaging for metastatic disease in early stage breast cancer. SpringerPlus. 2014; 3:176. https://doi.org/10.1186/2193-1801-3-176 PMID: 24790821

41. Simos D, Hutton B, Clemons M. Are Physicians Choosing Wisely When Imaging for Distant Metastases in Women With Operable Breast Cancer? J Oncol Pract. 2015; 11(1):62–8. https://doi.org/10.1200/JOP.2014.000125 PMID: 25392522

42. Jagsi R, Abrahamse P, Morrow M, Hawley ST, Griggs JJ, Graff JJ, et al. Patterns and Correlates of Adjuvant Radiotherapy Receipt After Lumpectomy and After Mastectomy for Breast Cancer. J Clin Oncol. 2010; 28(14):2396–403. https://doi.org/10.1200/JCO.2009.26.8433 PMID: 20351324

43. Bouchardy C, Rapiti E, Blagojevic S, Vlastos A-T, Vlastos G. Older female cancer patients: importance, causes, and consequences of undertreatment. J Clin Oncol. 2007; 25(14):1858–69. https://doi.org/10.1200/JCO.2006.10.4208 PMID: 17488984

44. Mislang AR, Cheung K-L, Hamaker ME, Kunkler I, Markopoulos C, Orecchia R, et al. Controversial issues in the management of older adults with early breast cancer. J Geriatr Oncol. 2017; 8(6):397–402. https://doi.org/10.1016/j.jgo.2017.05.004 PMID: 28602710

45. Hansen TM, Zellars RC. Treatment Minimization in Older Patients With Early-Stage Breast Cancer. Cancer J. 2017; 23(4):231–7. https://doi.org/10.1097/PPO.0000000000000272 PMID: 28731946

46. Ferrigni E, Bergom C, Yin Z, Szabo A, Kong AL. Breast Cancer in Women Aged 80 Years or Older: An Analysis of Treatment Patterns and Disease Outcomes. Clin Breast Cancer. 2019; 19(3):157–64. https://doi.org/10.1016/j.clbc.2019.01.007 PMID: 30819504

47. Kimmick G, Fleming ST, Sabatino SA, Wu X-C, Hwang W, Wilson JF, et al. Comorbidity burden and guideline-concordant care for breast cancer. J Am Geriatr Soc. 2014; 62(3):482–8. https://doi.org/10.1111/jgs.12687 PMID: 24512124

48. Rococo E, Mazouni C, Or Z, Mobillion V, Koon Sun Pat M, Bonastre J. Variation in rates of breast cancer surgery: A national analysis based on French Hospital Episode Statistics. Eur J Surg Oncol. 2016; 42(1):51–8. https://doi.org/10.1016/j.ejso.2015.09.020 PMID: 26490007
35. Fisher S, Gao H, Yasui Y, Dabbs K, Winget M. Treatment variation in patients diagnosed with early stage breast cancer in Alberta from 2002 to 2010: a population-based study. BMC Health Serv Res. 2015; 15:35. https://doi.org/10.1186/s12913-015-0680-z PMID: 25609420

36. Gligorov J, Krakowski I, Luporsi E, Namer M. [Recommandations pour la Pratique Clinique : Nice—Saint-Paul-de-Vence 2011 / « Cancers du sein : recommandations et veille bibliographique »]. Oncologie. 2011; 13(10–11).

37. Chatterjee A, Serniak N, Czerniecki BJ. Sentinel Lymph Node Biopsy in Breast Cancer: A Work in Progress. Cancer J. 2015; 21(1):7–10. https://doi.org/10.1097/PPO.0000000000000090 PMID: 25611773

38. Chagpar A, Babiera G, Aguirre J, Caropreso P, Hughes T, American College of Surgeons Communities. Variation in metastatic workup for patients with invasive breast cancer. Am J Surg. 2015; 210(6):1147–1154.e2; discussion 1153–1154. https://doi.org/10.1016/j.amjsurg.2015.06.032 PMID: 26518161

39. Simos D, Catley C, van Walraven C, Arnaout A, Booth CM, McInnes M, et al. Imaging for distant metastases in women with early-stage breast cancer: a population-based cohort study. Can Med Assoc J. 2015; 187(12):E387–97.

40. Simos D, Hutton B, Graham ID, Arnaout A, Caudrelier J-M, Mazzarello S, et al. Patient perceptions and expectations regarding imaging for metastatic disease in early stage breast cancer. SpringerPlus. 2014; 3:176. https://doi.org/10.1186/2193-1801-3-176 PMID: 24790821

41. Simos D, Hutton B, Clemons M. Are Physicians Choosing Wisely When Imaging for Distant Metastases in Women With Operable Breast Cancer? J Oncol Pract. 2015; 11(1):62–8. https://doi.org/10.1200/JOP.2014.000125 PMID: 25392522

42. Jagsi R, Abrahamse P, Morrow M, Hawley ST, Griggs JJ, Graff JJ, et al. Patterns and Correlates of Adjuvant Radiotherapy Receipt After Lumpectomy and After Mastectomy for Breast Cancer. J Clin Oncol. 2010; 28(14):2396–403. https://doi.org/10.1200/JCO.2009.26.8433 PMID: 20351324

43. Bouchardy C, Rapiti E, Blagojevic S, Vlastos A-T, Vlastos G. Older female cancer patients: importance, causes, and consequences of undertreatment. J Clin Oncol. 2007; 25(14):1858–69. https://doi.org/10.1200/JCO.2006.10.4208 PMID: 17488984

44. Mislang AR, Cheung K-L, Hamaker ME, Kunkler I, Markopoulos C, Orecchia R, et al. Controversial issues in the management of older adults with early breast cancer. J Geriatr Oncol. 2017; 8(6):397–402. https://doi.org/10.1016/j.jgo.2017.05.004 PMID: 28602710

45. Hansen TM, Zellars RC. Treatment Minimization in Older Patients With Early-Stage Breast Cancer. Cancer J. 2017; 23(4):231–7. https://doi.org/10.1097/PPO.0000000000000272 PMID: 28731946

46. Ferrigni E, Bergom C, Yin Z, Szabo A, Kong AL. Breast Cancer in Women Aged 80 Years or Older: An Analysis of Treatment Patterns and Disease Outcomes. Clin Breast Cancer. 2019; 19(3):157–64. https://doi.org/10.1016/j.clbc.2019.01.007 PMID: 30819504

47. Kimmick G, Fleming ST, Sabatino SA, Wu X-C, Hwang W, Wilson JF, et al. Comorbidity burden and guideline-concordant care for breast cancer. J Am Geriatr Soc. 2014; 62(3):482–8. https://doi.org/10.1111/jgs.12687 PMID: 24512124

48. Rococo E, Mazouni C, Or Z, Mobillion V, Koon Sun Pat M, Bonastre J. Variation in rates of breast cancer surgery: A national analysis based on French Hospital Episode Statistics. Eur J Surg Oncol. 2016; 42(1):51–8. https://doi.org/10.1016/j.ejso.2015.09.020 PMID: 26490007