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Abstract

Objective

A decrease in advanced breast cancer incidence is considered an early indicator of breast cancer mortality reduction in a screening programme. We describe trends in breast cancer incidence according to tumour size and age in three French administrative areas, where an organized screening programme was implemented during the 1990s.

Methods

Our study included all 28,092 invasive breast cancers diagnosed from 2000 to 2010 in women living in three areas (Hérault, Isère, Loire-Atlantique). Age, year of diagnosis, and size of tumour at diagnosis was provided by the three area cancer registries. Poisson regression models were fitted to estimate changes in incidence over time, after adjustment for age and administrative area.

Results

From 2000 to 2010, the incidence rate of large (tumour size >20 mm) breast cancer linearly decreased in women aged 50–74 (target age of the screening programme) from 108.4 to 84.1/100,000 (annual percent change = −1.9%, p < 0.001). No change in large breast cancer incidence rate was found in women aged 20–49, or older than 74.

Conclusions

A decreasing trend in incidence of large tumour size breast cancer in the target age of the screening programme is demonstrated for the first time in France. The overall 20.9% linear decrease over 11 years in these three areas is encouraging and should be closely monitored and extended to other areas of France, where the screening programme was generally implemented only in 2004.

Keywords

Breast cancer tumour size incidence trends population-based screening programme

Introduction

The balance between harms and benefits of screening for breast cancer (BC) is still under debate.^1–4 Determining the impact of mammographic screening on BC mortality in general populations is a challenge, because of methodological issues. Screening is assumed to allow BC diagnosis at an earlier stage and, consequently, to lower BC mortality. An approximate proportional decrease in risk of advanced BC (either TNM stage II+ or tumour size >20 mm) and in BC mortality has been shown in several randomized trials. A decrease in advanced BC incidence in the target population is considered an early indicator of BC mortality reduction.^5–9 In several countries, results are contrasted regarding the evolution of advanced-stage BC incidence.^10–18 However, the effectiveness of a screening programme at national level will be determined not only by its design and ability to detect small tumours but also by the cultural, medical, and economic context determining programme attendance and also timeliness and accurate treatment.

In France, the BC screening programme was gradually implemented from 1989 in pilot screening areas, until implementation across the entire country in 2004.¹⁹ After the introduction of the screening programme in the pilot areas, a decreasing trend of advanced BC incidence was expected in the target age group of women (50–74). No information has been available in France regarding the assessment of the screening programme based on advanced-stage BC.

We aimed to describe trends in BC incidence, according to tumour size, in women aged 50–74 compared with women in other age groups in the general population, in three pilot screening areas covered by a population-based cancer registry in France.

Methods

This observational population-based study was conducted in three screening pilot areas (Hérault, Isère, Loire-Atlantique) with 3.6 million inhabitants, covered by cancer registries, and where the screening programme was implemented before 2000. All first invasive breast carcinomas diagnosed from 2000 to 2010 in women living in these areas were recorded by the three cancer registries and included in the study.

French cancer registries routinely collect data on cases from pathological laboratories, departments of medical data processing and clinical services of public and private hospitals, health insurance funds, and medical practitioners. Data are recorded according to the European Network of Cancer Registries recommendations. The quality and completeness of these population-based registries are certified every four years in an audit by the French National Institute of Health and Medical Research and the French Institute for Public Health Surveillance.

Because mammographic screening aims to detect breast tumours while they are small, the size of invasive cancer was chosen as the indicator of cancer stage. The size for distinguishing early and advanced BC was 20 mm, corresponding to the threshold between T1 and T2 classification (Union for International Cancer Control TNM classification) recorded in cancer registries.²⁰ We defined T2+ BC as BC with a tumour size >20 mm and T1 BC as BC with a tumour size ≤20 mm, whatever lymph node involvement or distant metastasis. In situ carcinoma, lymphoma, and sarcoma were excluded. Women with no available tumour size (n = 991) were also excluded from analyses.

The analyses were performed in three age-groups: the target age group for organized screening (50–74), and the youngest (20–49) and oldest women (75 and over). Incidence rates were calculated using the French female population from official census data of the three areas for each age group, and standardized using the world standard population, which was truncated according to the corresponding age group. Poisson regression models were fitted to estimate changes in incidence over time, after adjustment for age and administrative area, from which we derived annual percent changes (APCs) and 95% confidence intervals (CIs). Stata SE11 was used.²¹

Results

Of the 28,092 BC cases included in the study, 58.8% were diagnosed in women aged 50–74 (Table 1). The distribution of BCs by tumour size was concordant in the three areas, with an average 27.8% T2+ BCs in women aged 50–74. T2+ BC was more frequent in the youngest (aged <50) and oldest (aged >74) age groups, accounting, respectively, for 36.8% and 54.0% of BCs.

Table 1.

Breast cancer characteristics according to age group (2000–2010).

	<50	50–74	>74	All ages
	n = 6691	n = 16,509	n = 4892	n = 28,092
Age (years)	N (%)	N (%)	N (%)	N (%)
Tumour size
T1	4227 (63.2)	11,925 (72.2)	2252 (46.0)	18,404 (65.5)
T2+	2464 (36.8)	4584 (27.8)	2640 (54.0)	9688 (34.5)
Missing = exclusion criteria
Lymph node involvement
N0	3965 (60.6)	11,025 (68.6)	2706 (63.3)	17,696 (65.8)
N+	2583 (39.4)	5050 (31.4)	1572 (36.7)	9205 (34.2)
Missing	143	434	614	1191
Distant metastasis
M0	6247 (96.5)	15,255 (95.8)	3932 (91.3)	25,434 (95.3)
M+	227 (3.5)	666 (4.2)	375 (8.7)	1268 (4.7)
Missing	217	588	585	1390
Stage
I	3011 (45.3)	9111 (56.0)	1568 (33.6)	13,690 (49.6)
II+	3635 (54.7)	7161 (44.0)	3104 (66.4)	13,900 (50.4)
Missing	45	237	220	502

From 2000 to 2010, the incidence rate of T2+ BC steadily decreased, by 20.9% on average (APC = −1.9%, p < 0.001), in women aged 50–74, from 108.4 to 84.1 per 100,000 women, whereas a stable incidence rate of T2+ BC was observed in women aged 20–49, and those older than 74 (Table 2, Figure 1). In the whole population of women aged 50–74, the absolute decrease was 24 T2+ BC cases per 100,000 women from 2000 to 2010. The diminishing trend of T2+ BC incidence was stronger among women aged 50–74 in areas with a higher participation rate during the study period; the participation rate and APC were, respectively, 55% and −2.7% (95%CI, −4.1 to −1.2) in Loire-Atlantique, 41% and −1.9% (95%CI, −3.5 to −0.2) in Hérault, and 32% and −0.9% (95%CI, −2.5 to 0.8) in Isère (see Figure 2 for participation rate; sources: management structures of organized screening, in the three areas covered by the study).

Table 2.

Breast cancer (BC) incidence trend according to tumour size at diagnosis and age group (2000–2010).

Age (years)	N	ASR	APC	95%CI	p
<50
T1 BC	4227	48.7	+0.8	−0.1, +1.8
T2+ BC	2464	28.6	+1.0	−0.2, +2.3
Total	6691	77.4	+0.9	+0.1, +1.7	*
50–74
T1 BC	11,925	237.0	−0.3	−0.8, +0.3
T2+ BC	4584	90.2	−1.9	−2.8, −1.0	***
Total	16,509	327.2	−0.7	−1.2, −0.2	**
>74
T1 BC	2252	127.0	+1.9	+0.6, +3.3	**
T2+ BC	2640	137.1	−0.8	−2.0, +0.4
Total	4892	264.1	+0.4	−0.5, +1.3

ASR: age standardized rate per 100,000; APC: annual percent change (%), with adjustment for age and administrative area.

p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001; otherwise not significant.

Figure 1.

Breast cancer (BC) incidence trend according to tumour size at diagnosis (2000–2010).

Figure 2.

Breast organized screening coverage in the studied area (2000–2010).

Contrary to the steady and linear 20.9% decrease of T2+ BC over the 11 years of the study, the evolution of T1 BC in women aged 50–74 followed an increasing trend until 2003, a decreasing trend until 2006, and stabilized thereafter (Figure 1). In further contrast, in women aged under 50, the overall incidence rate steadily rose by 0.9% a year for all-stage BC (Table 2). In women older than 74, no increase in incidence rates of T2 + BC was observed, whereas early stage BCs were still in progression (+1.9%).

We also conducted complementary analyses, in which we considered advanced stage II+ BCs to be tumours of size >20 mm or with lymph node involvement or distant metastasis (T2+ or N+ or M+), according to the Union for International Cancer Control classification. Early stage I cancers had tumour size ≤20 mm, with neither lymph node involvement nor distant metastasis (T1 N0 M0). Distribution of stage is described in Table 1. Main tendency results were quite similar; in particular, a steady linear decreasing trend of stage II+ BC incidence was observed in women aged 50–74 (APC = −2.0%, p < 0.001) (Table 3).

Table 3.

Breast cancer (BC) incidence trend according to stage at diagnosis and age group (2000–2010).

Age (years)	N	ASR	APC	95%CI	p
<50
Early BC (stage I)	3011	34.7	+1.5	+0.4,+2.7	**
Advanced BC (stage II+)	3688	42.8	+0.3	−0.7,+1.3
Total	6699	77.5	+0.9	+0.1,+1.6	*
50–74
Early BC (stage I)	9111	180.4	+0.7	+0.1,+1.4	*
Advanced BC (stage II+)	7331	145.5	−2.0	−2.7,−1.3	***
Total	16,442	325.9	−0.5	−1.0,0	0.054
>74
Early BC (stage I)	1568	90.1	+3.5	+1.9,+5.2	***
Advanced BC (stage II+)	3256	170.7	+0.1	−1.0,+1.2
Total	4824	260.8	+1.2	+0.3,+2.1	*

ASR: age standardized rate per 100,000; APC: annual percent change (%), with adjustment for age and administrative area.

p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001; otherwise not significant.

Discussion

This study demonstrates a 20.9% steady decrease of T2+ BC incidence from 2000 to 2010 in French women aged 50–74, in areas where a screening programme was implemented before 2000. This is the first time that a diminishing trend has been highlighted in France. The reduction of advanced BC, defined as T2+ as well as stage II+, has been proven to be correlated to the reduction of BC mortality in randomized trials.^6–8 The size of invasive cancer is strongly correlated to nodal status, and its measurement has remained stable over time (contrary to nodal involvement determination). We used complementary analyses to address potential limitations of this definition. Decreasing trend of advanced BC was confirmed if advanced BC was defined as stage II+ (>20 mm or N+ or M+).

Differences in design, study period, and definition of late-stage BC make it difficult to compare studies; however, other studies have also found a reduction in advanced BC incidence after the introduction of organized mammography screening. In Italy, a strong decrease was observed, with the incidence rate ratio around 0.8 between the observed rate and the expected rate of advanced T2+ BC eight years after organized screening implementation.¹⁰ In Finland, East Anglia, US, The Netherlands, and Sweden, decreasing trends in late-stage BC have also been observed.^11–15 Other studies failed to evidence a reduction in advanced BC incidence, sustaining controversy on the efficacy of organized screening.^16–18 These discrepant study results highlight the methodological difficulties to take into account possible bias in the choice of the period, the reference population, and particularly the hypothesis regarding the unknown underlying trend of BC incidence which, if increasing, may mask a potential decrease in advanced BC incidence. However, evolution of advanced stage incidence is not the only indicator of efficacy of an organized screening programme that may show favourable outcomes, even without reduction in advanced BC incidence.²²

Organized screening was introduced during the 1990s in the three areas of this study, but participation rates were low before 2000 and were still in progression during the study period. Although the results of this observational study must be interpreted with caution, some facts could be consistent with a possible impact of the screening programme on the reduction of BC diagnosed at an advanced stage in women aged 50–74. The drop in T2+ BC in women aged 50–74 contrasted with the stability of T2+ BC in the oldest and youngest groups of women. In older women, the stability of T2+ BC while T1 BC incidence was still in progression would be concordant with an impact of the screening programme in a context of growing underlying trend of incidence. It can also be argued that the higher the rate of participation in the screening programme in one area, the greater the decrease of T2+ BC incidence. Contrary to the nonlinear evolution of T1 BC incidence rate in the 50–74 age group, the changes in the T2+ BC incidence rate were linear throughout the study period. Most particularly, the evolution of T1 BC in women aged 50–74 followed a well-known pattern described in many countries, including France, which has already been discussed in relation to the decreasing prescription of hormone replacement therapy.^23,24 The decrease in T1 BC incidence was restricted to the 2003–2006 period; a stabilization occurred after 2006 when hormone replacement therapy use stabilized at a lower rate. The extent to which overdiagnosis could explain the changes in T1 BC remains under debate.^25–27 In this study, the advanced T2+ BC incidence reduction is possibly underestimated for two main reasons. First, rather than remaining steady, the underlying BC incidence may have increased. The increasing BC incidence observed in younger women in our study (+0.9%/year), as well as in other studies during a longer period (1990–2010), would be consistent with this hypothesis.^28,29 Second, many women delay or skip a screening session (the re-attendance rate for the next screening round was estimated at around 80% in Isère in 2003), losing the benefit of screening every two years, and thus exposing themselves to a BC diagnosed at a more advanced stage.³⁰ Only three areas were included in this study, and these may not be representative of the whole of France. However, they were pilot areas for screening programme implementation before 2000, whereas the screening programme was introduced in most other areas only in 2004, too recently for an adequate assessment of trends.

This observational study does not allow causal inference, and it cannot ascertain whether, or which part of, the overall linear decrease of T2+ BC incidence in the target age group of the screening programme was related to the screening programme itself. However, this result is encouraging, and further studies are needed in other geographic areas where organized screening was introduced after 2004.

Footnotes

Acknowledgements

We thank Jacques Estève for assistance in methodology and interpretation of the results. We are grateful for the generous assistance of the pathologists, oncologists, Departments of Medical Data Processing of public and private hospitals, and medical practitioners as well as the medical services of the national health insurance programme that routinely provide data to the cancer registries. The authors also thank Linda Northrup (English Solutions) for translation and editorial assistance.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Grant sponsors for routine collection of data: National Cancer Institute (INCa), French Institute for Public Health Surveillance (InVS), local public institutions (Conseil Régional, Conseil Départemental), and Ligue contre le cancer.

References

Paci

Broeders

Hofvind

et al.

European breast cancer service screening outcomes: a first balance sheet of the benefits and harms. Cancer Epidemiol Biomarkers Prev 2014; 23: 1159–1163.

Løberg

Lousdal

Bretthauer

et al.

Benefits and harms of mammography screening. Breast Cancer Res 2015; 17: 63–63.

Smith

. The value of modern mammography screening in the control of breast cancer: understanding the underpinnings of the current debates. Cancer Epidemiol Biomarkers Prev 2014; 23: 1139–1146.

Independent UK Panel. The benefits and harms of breast cancer screening: an independent review. Lancet 2012; 380: 1778–1786.

Smith Robert

. IARC handbooks of cancer prevention: breast cancer screening, Lyon: IARC, 2002.

Tabár

Gad

Holmberg

et al.

Reduction in mortality from breast cancer after mass screening with mammography. Lancet 1985; 325: 829–832.

Duffy

Tabar

Vitak

et al.

The relative contributions of screen-detected in situ and invasive breast carcinomas in reducing mortality from the disease. Eur J Cancer 2003; 39: 1755–1760.

Norman

Localio

Zhou

et al.

Benefit of screening mammography in reducing the rate of late-stage breast cancer diagnoses (United States). Cancer Causes Control 2006; 17: 921–929.

Tabár

Yen

AM-F

WY-Y

et al.

Insights from the Breast Cancer Screening Trials: how screening affects the natural history of breast cancer and implications for evaluating service screening programs. Breast J 2015; 21: 13–20.

10.

Foca

Mancini

Bucchi

et al.

Decreasing incidence of late-stage breast cancer after the introduction of organized mammography screening in Italy: screening and late-stage breast cancer. Cancer 2013; 119: 2022–2028.

11.

Anttila

Sarkeala

Hakulinen

et al.

Impacts of the Finnish service screening programme on breast cancer rates. BMC Public Health 2008; 8: 38–38.

12.

McCann

Stockton

Day

. Breast cancer in East Anglia: the impact of the breast screening programme on stage at diagnosis. J Med Screen 1998; 5: 42–48.

13.

Swedish Organised Service Screening Evaluation Group. Effect of mammographic service screening on stage at presentation of breast cancers in Sweden. Cancer 2007; 109: 2205–2212.

14.

Helvie

Chang

Hendrick

et al.

Reduction in late-stage breast cancer incidence in the mammography era: implications for overdiagnosis of invasive cancer: reduction in late-stage breast cancer. Cancer 2014; 120: 2649–2656.

15.

Fracheboud

Otto

van Dijck

et al.

Decreased rates of advanced breast cancer due to mammography screening in The Netherlands. Br J Cancer 2004; 91: 861–867.

16.

Bleyer

Welch

. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 2012; 367: 1998–2005.

17.

Nederend

Duijm

Voogd

et al.

Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study. Breast Cancer Res 2012; 14: R10–R10.

18.

Hofvind

Sørum

Thoresen

. Incidence and tumor characteristics of breast cancer diagnosed before and after implementation of a population-based screening-program. Acta Oncol Stockh Swed 2008; 47: 225–231.

19.

Ministre de la Santé et de la Solidarité. Arrêté du 29 septembre 2006 relatif aux programmes de dépistage des cancers. Available at: www.legifrance.gouv.fr/affichTexte.do?cidTexte=JORFTEXT000000460656 (2006, accessed 12 July 2016).

20.

Sobin LH, Gospodarowicz MK, Wittekind C, et al. (eds). TNM classification of malignant tumours. 7th ed. Chichester: Wiley-Blackwell, 2010.

21.

StataCorp. Stata statistical software: release 11, College Station, TX: StataCorp LP, 2009.

22.

Hofvind

Ursin

Tretli

et al.

Breast cancer mortality in participants of the Norwegian Breast Cancer Screening Program: breast CA mortality in screened women. Cancer 2013; 119: 3106–3112.

23.

Molinié

Vanier

Woronoff

et al.

Trends in breast cancer incidence and mortality in France 1990-2008. Breast Cancer Res Treat 2014; 147: 167–175.

24.

Séradour

Allemand

Weill

et al.

Sustained lower rates of breast cancer incidence in France in 2007. Breast Cancer Res Treat 2010; 121: 799–800.

25.

Esserman

Shieh

Thompson

. Rethinking screening for breast cancer and prostate cancer. JAMA 2009; 302: 1685–1692.

26.

Puliti

Duffy

Miccinesi

et al.

Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen 2012; 19(Suppl. 1): 42–56.

27.

Drukker

Schmidt

Rutgers

EJT

et al.

Mammographic screening detects low-risk tumor biology breast cancers. Breast Cancer Res Treat 2014; 144: 103–111.

28.

Leclère

Molinié

Trétarre

et al.

Trends in incidence of breast cancer among women under 40 in seven European countries: a GRELL cooperative study. Cancer Epidemiol 2013; 37: 544–549.

29.

Viel

J-F

Rymzhanova

Fournier

et al.

Trends in invasive breast cancer incidence among French women not exposed to organized mammography screening: an age-period-cohort analysis. Cancer Epidemiol 2011; 35: 521–525.

30.

Seigneurin

Exbrayat

Labarère

et al.

Association of diagnostic work-up with subsequent attendance in a breast cancer screening program for false-positive cases. Breast Cancer Res Treat 2011; 127: 221–228.

Breast cancer incidence: Decreasing trend in large tumours in women aged 50–74

Abstract

Objective

Methods

Results

Conclusions

Keywords

Introduction

Methods

Results

Discussion

Footnotes

Acknowledgements

Declaration of conflicting interests

Funding

References