Using data from the Geneva Cancer Registry, we found that in 2002-2004, breast cancer incidence in women aged 25-39 years increased by 46.7% per year (95% CI: 7.1-74.0, P=0.015), which surveillance or detection bias may not fully explain

A Morabia

A-P Sappino

BC Yankaskas

C Bouchardy

CM Magnusson

E Rapiti

G Fioretta

G Vlastos

GA Colditz

H M Verkooijen

I Neyroud-Caspar

J-F Delaloye

JM Lutz

KB Michels

M Forni

MC Costanza

MD Miller

P Chappuis

P Schaefer

S Balmer Majno

Y Wespi

PubMed

10.1038/sj.bjc.6603783British Journal of Cancer96111743-174

Bouchardy, C.

Fioretta, G.

Verkooijen, H.M.

Neyroud-Caspar, I.

Rapiti, E.

Vlastos, G.

Schaefer, P.

Delaloye, J.-F.

Balmer, Majno S.

Wespi, Y.

Forni, M.

Chappuis, P.

Sappino, A.-P.

ScholarBank@NUS

Recent increase of breast cancer incidence among women under the age of forty

Crossref

Bouchardy,  C.

Fioretta,  G.

Verkooijen,  H. M.

Vlastos,  G.

Schaefer,  P.

Delaloye,  J. F.

Neyroud-Caspar,  I.

Balmer Majno,  S.

Wespi,  Y.

Forni,  M.

Chappuis,  P.

Sappino,  A. P.

Rapiti,  E.

Serveur académique lausannois

Short CommunicationRecent increase of breast cancer incidence among women underthe age of fortyC Bouchardy*,1, G Fioretta1, HM Verkooijen1,2, G Vlastos3, P Schaefer3, J-F Delaloye4, I Neyroud-Caspar1,S Balmer Majno5, Y Wespi6, M Forni6, P Chappuis7, A-P Sappino7 and E Rapiti11Geneva Cancer Registry, Institute for Social and Preventive Medicine, University of Geneva, 55, bd de la Cluse, 1205 Geneva, Switzerland; 2Departmentof Community, Occupational and Family Medicine, National University of Singapore, 16 Medical Drive, 117597, Singapore; 3Senology and SurgicalGynecologic Oncology Unit, Department of Gynecology and Obstetrics, Geneva University Hospitals, Bd de la Cluse 32, 1205 Geneva, Switzerland;4Department of Gynecology and Obstetrics, Vaud University Hospitals, CHUV, Rue du Bugnon 21, 1005 Lausanne, Switzerland; 5Division of Radio-Oncology, Geneva University Hospitals, Av. de la Roseraie 53, 1205 Geneva, Switzerland; 6Association of Physicians of the canton of Geneva, Rue Micheli-du-Crest 12, 1205 Geneva, Switzerland; 7Division of Oncology, Department of Medicine, Geneva University Hospitals, Rue Micheli-du-Crest 24,1211Geneva 14, SwitzerlandUsing data from the Geneva Cancer Registry, we found that in 2002–2004, breast cancer incidence in women aged 25–39 yearsincreased by 46.7% per year (95% CI: 7.1–74.0, P¼ 0.015), which surveillance or detection bias may not fully explain.British Journal of Cancer (2007) 96, 1743–1746. doi:10.1038/sj.bjc.6603783 www.bjcancer.comPublished online 29 May 2007& 2007 Cancer Research UKKeywords: breast cancer; young patients; trend; incidence rates; cancer registry; population-based studyHealth professionals and patient support groups in Geneva,Switzerland, have recently expressed concern about an apparentlyincreasing number of very young breast cancer patients. Owing tothe average 2-year delay in cancer registration, we have only nowbeen able to investigate this observation using incidence data up tothe year 2004 among women residents in Geneva.MATERIALS AND METHODSThe Geneva cancer registry, functional since 1970 and covering thewhole population of the canton (approximately 435 000 inhabi-tants), is considered comprehensive with a low percentage (o2%)of cases recorded from death certificates only (Bouchardy, 1997).Trained staff systematically abstract data from reports of allpathology laboratories and public hospitals. Private practitionersregularly fill out questionnaires to complete missing clinical andtherapeutic data; death certificates are systematically consulted.We included all incident invasive breast cancer cases diagnosedin the resident population of the canton between 1995 and 2004(n¼ 3608), with the population at risk considered as the residentpopulation at the middle of each relevant year, obtained from theCantonal Population Office. We calculated annual incidence ratesfor five age groups: 25–39, 40–49, 50–69, 70–79, and X80 years.Trends in age-specific annual incidence rates were calculated bylog-linear Poisson regression implemented in the generalisedlinear interactive modelling statistical package (Francis et al,1993). We calculated mean annual rates of increase over the wholeperiod to test for a continuous progressive increase and calculatedthe mean annual rates for the last 3-year period only to test for arecent, sudden increase. For women aged 25–39 years, wecompared patient and tumour characteristics before and whenthe increase occurred by w2 test for heterogeneity.Variables of interest included family history of breast or ovariancancer (positive if one first-degree or two second-degree relativeswere affected, and negative), method of detection (mammographyor clinical screening, breast self-examination, symptoms or other),modalities of diagnostic assessment (clinical status, mammo-graphy or ultrasound, magnetic resonance imaging (MRI): yes vsno), histological type (ductal: ICD-O code 8500, lobular: ICD-0code 8520 and 8522, and other), differentiation (grades I–III, andunknown coded according to the International Classification ofDiseases for Oncology, ICD-O (ICD-O International Classificationof Diseases for Oncology, 1976)), oestrogen and progesteronereceptor status (positive (if X10% of cells expressed receptors),negative, and unknown), mean pathological tumour size (in mm),and stage (coded according to the tumour, node and metastasisTNM classification (TNM Classification of malignant tumours,1992)). We used the pathologic pTNM classification system or,when absent, the clinical cTNM classification. Tumour stage wasconsidered as stage I (T1 and N0), stage II (T0 or T1 and N1, T2and N0 or N1, T3 and N0), stage III (T0 or T1 or T2 and N2, T3 andN1 or N2, T4 and any N, any T and N3), stage IV (M1) andunknown. We also examined the proportion of tumours withclinical T0 N0 M0.RESULTSFor women aged 25–39 years, breast cancer rates were steady until2002 and increased sharply thereafter, being 19.7 per 100 000 in1995, rising to 53.9 per 100 000 in 2004 (Figure 1). Table 1 presentsresults of trend tests for the period 1995– 2004 (middle columns)Received 8 February 2007; revised 2 April 2007; accepted 13 April 2007;published online 29 May 2007*Correspondence: Dr C Bouchardy;E-mail: Christine.BouchardyMagnin@imsp.unige.chBritish Journal of Cancer (2007) 96, 1743 – 1746& 2007 Cancer Research UK All rights reserved 0007 – 0920/07 $30.00www.bjcancer.comEpidemiologyand for the last 3-year period 2002–2004 (right column). The meanannual increase was 8.7% (95% CI: 2.8–15.0, P¼ 0.003) over thewhole period. The entire increase occurred in the last 3-year period(2002–2004) with a mean annual increase of 46.7% (95% CI: 7.1–74.0%, P¼ 0.015). Cancers at ages 25 –39 represented 3.4% of allbreast cancers in 1995 and 7.2% in 2004 (P¼ 0.032). Also, since1970 (when cancer registration started in Geneva) no such increasehas been observed (data not shown). For the other age groups,incidence remained fairly stable, except for women aged 50– 69years among whom it increased at an average of 2.6% per year,from 1998 to 2002, when it stabilised (Table 1, Figure 1).Table 2 shows tumour characteristics among women aged 25– 39years in 1995– 2001 and 2002– 2004. We found a significantincrease in diagnoses diagnosed by MRI. In particular, 26% ofbreast cancers in young women were diagnosed by MRI in 1995–2001 compared with 48% in 2002– 2004 (P¼ 0.006). Screen-detected cancers increased non-significantly from 9 to 19%. Theproportion of stage I cancers slightly decreased from 40 to 33%,whereas the proportion of stage II cancers remained relativelyconstant around 45%. Only three women had non-clinical T0 N0tumours, one in the first and two in the second period. The meantumour size remained unchanged over the whole study period, at21 mm in 1995–2001 and 20 mm in 2002–2004 (P¼ 0.817). Weobserved no increase in the proportion of young patients with apositive familial history of breast cancer.DISCUSSIONIn Geneva, breast cancer incidence in women aged o40 years hasrecently doubled. This increase may be partly explained by ahigher screening frequency of younger women and betterWomen aged 25–39 years Year 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004Patients N 10 13 15 11 15 12 16 13 21 29 Women at risk N 50 762 51 117 51 125 51 116 51 342 51 769 52 350 52 967 53 606 53 831 Incidence rates 19.7 25.4 29.3 21.5 29.2 23.2 30.6 24.5 39.2 53.9 per 100 000 11010010001995 1996 1997 1998 1999 2000 2001 2002 2003 2004Incidence rates (1/100 000)80+70–7950–6940–4925–39Figure 1 Trends(logarithmic scale) in annual breast cancer incidence rates by age group in Geneva, Switzerland.Table 1 Mean annual increase of breast cancer incidence rates by age group for the whole study period and for the last 3-year period and P-value fortrend testsIncidence rates per 100 000 Trend test for the whole study period 1995–2004aTrend test for the last 3-year periodof the study 2002–2004bAge 1995 2004 Mean annual increase (95% CI) P-value Mean annual increase (95% CI) P-value25–39 19.7 53.9 +8.7 (2.8–15.0) 0.003 +46.7 (7.1–100.8) 0.01540–49 187.3 198.8 0.6 (2.8–3.4) 0.700 +5.4 (11.6–27.7) 0.55550–69 312.4 400.2 +2.6 (1.0–4.2) 0.001 1.7 (11.7–8.3) 0.73770–79 332.6 383.5 0.4 (2.3–3.3) 0.756 +11.0 (7.1–32.6) 0.247X80 330.7 381.4 +0.9 (2.5–4.5) 0.590 +3.1 (16.9–27.8) 0.781CI¼ confidence interval. aPoisson regression testing trends of annual incidence rates during the period 1995–2004. bPoisson regression testing trends of annual incidence ratesduring the period 2002–2004.Breast cancer in young womenC Bouchardy et al1744British Journal of Cancer (2007) 96(11), 1743 – 1746 & 2007 Cancer Research UKEpidemiologysurveillance and recognition of familial risk factors. Improvedtumour detection through advances in imaging techniques mayalso be involved, since in 1995–2001 less than 30% of breast cancerdiagnoses in young women involved MRI compared with nearly50% in 2002–2004 (P¼ 0.006).Nevertheless, these detection biases seem unlikely to explainfully the observed incidence increase. Screening and improvementin diagnostic techniques should lead to a shift in stage distributiontowards earlier stages, whereas in our population, this did notchange significantly, and the proportion of clinically palpabletumours remained constant. The screening programme imple-mented in Geneva 10 years ago targets women aged 50– 69 years,and screening for breast cancer in women o40 years is rare (Lutzet al, 2000). Furthermore, the proportion of patients reporting apositive family history has remained relatively stable around 30%between the two periods. We can also reasonably rule out anincrease in fortuitous discovery of contralateral breast cancer asonly two women were diagnosed with synchronous breast cancerin 2002 and 2003 respectively.Although significant, our observation is based on only 63patients diagnosed in 2002– 2004, and should be interpreted withcaution. With respect to any change in population estimates, theyoung resident female population grew smoothly over the studyperiod, with no sudden increase in 2002– 2004 (Figure 1). Amongother cancer sites of women aged 25– 39 years, we found asignificant increase of melanoma (mean annual increase of 6.9%;95% CI: 0.3–13.8, P¼ 0.038) starting early in the study period, butthis is already a well-documented phenomenon in Switzerland(Association of Swiss Cancer Registries (ASCR), 2002).Other reasons should be explored to explain this increase inbreast cancer incidence in younger women. Most known breastcancer risk factors, including nulliparity or later age at first full-term pregnancy, early menarche, dietary habits, alcohol intake,and lack of physical activity, apply at all ages. However, some otherfactors, such as family history of breast and/or ovarian cancer, inutero exposure, oral contraceptive use, smoking, and breastradiation are more relevant to young women (Yankaskas, 2005;Colditz et al, 2006).In Geneva, prevalence of obesity has increased amongadolescents and young females (Morabia and Costanza, 2005),but, in contrast to post-menopausal women, it appears to beprotective against breast cancer in young women (Bouchardy et al,1990; Magnusson et al, 2005; Michels et al, 2006). Smoking stillseems to be increasing among women in Geneva and, comparedwith older women, young women begin smoking cigarettes at amuch earlier age and are heavier smokers (Costanza et al, 2006).Table 2 Comparison of tumour assessment and characteristics of breast cancer patients aged o40 years before and after the increase began1995–2001 2002–2004Patient and tumour characteristics Number (%) Number (%) P-value for heterogeneity testAge at diagnosis25–29 years 6 (7) 6 (10) 0.52330–34 years 32 (35) 17 (27)35–39 years 54 (59) 40 (64)Method of detectionScreening 8 (9) 12 (19) 0.168Breast self-examination 66 (72) 40 (64)Symptoms, other 18 (20) 11 (18)Diagnostic assessmentClinical statusa 81 (88) 58 (92) 0.419Mammography or ultrasounda 80 (87) 56 (88) 0.719MRIa 24 (26) 30 (48) 0.006Family historyNegative 64 (70) 41 (65) 0.557Positive 28 (30) 22 (35)StageI 37 (40) 21 (33) 0.673II 41 (45) 27 (43)III 7 (8) 9 (14)IV 4 (4) 3 (5)Unknown 3 (3) 3 (5)HistologyDuctal 81 (88) 60 (95) 0.078Lobular 0 (0) 1 (2)Other 11 (12) 2 (3)GradeI 15 (16) 8 (13) 0.217II 33 (36) 33 (52)III 38 (41) 20 (32)Unknown 6 (7) 2 (3)Oestrogen receptor statusNegative 33 (36) 18 (29) 0.630Positive 56 (61) 43 (68)Unknown 3 (3) 2 (3)Progesterone receptor statusNegative 37 (40) 25 (40) 0.997Positive 52 (57) 36 (57)Unknown 3 (3) 2 (3)Total 92 (100) 63 (100)MRI¼magnetic resonance imaging. aBinary variables classified as yes vs no.Breast cancer in young womenC Bouchardy et al1745British Journal of Cancer (2007) 96(11), 1743 – 1746& 2007 Cancer Research UKEpidemiologyNo causal relation between breast cancer and smoking is generallyaccepted although any impact could be greater on young women(Miller et al, 2007). In this study, we can exclude an associationwith previous cancer treatment, given that only one woman was soaffected (bilateral ovarian cancer).In comparison, for Europe and the United States, we found norecent or sudden increase in breast cancer incidence amongwomen under 40 years in the two main public-use cancer registrydata sets, the Surveillance Epidemiology and End Results (SEER)and Cancer Incidence in Five Continents (CIF) (InternationalAgency for Research on Cancer (IARC), 2002; National CancerInstitute (NCI), 2004). However, the latest available years were1997 for CIF and 2003 for SEER.In conclusion, we observed a significant increase in youngbreast cancer patients. At present, we cannot definitively rule outan increased surveillance and detection bias and we cannotconfidently conclude a sustained increase. Careful surveillance ofrecent trends of breast cancer incidence is required for youngwomen. If other population-based cancer registries confirm thistrend, further research on breast cancer risk factors, including anyacting in utero and early in life, would be indicated.ACKNOWLEDGEMENTSWe thank Stina Blagojevic for her technical and editorialassistance, Arnaud Merglen for review and comments, AngelaGrezet and the patients from the Comite´ Qualite´ de vie et Cancerdu sein for their helpful feedback, and the Cancer registry team forproviding data and support. We also thank the three reviewers ofthe JAMA for their very helpful comments on a previous version ofthe manuscript.Dr HM Verkooijen was financially supported by PROSPER GrantNo. 3233-069350 from the Swiss National Science Foundation.REFERENCESAssociation of Swiss Cancer Registries (ASCR) 2002 Available from: URL:www.asrt.ch [cited 2007]Bouchardy C (1997) Switzerland, Geneva. In: Cancer Incidence in FiveContinents, vol. VII Parkin DM, Whelan SL, Ferlay J, Raymond L, YoungJ (eds). 666 – 669. Lyon: International Agency for Research on CancerBouchardy C, Leˆ MG, Hill C (1990) Risk factors for breast cancer accordingto age at diagnosis in a French case-control study. J Clin Epidemiol 43(3):267 – 275Colditz GA, Baer HJ, Tamimi RM (2006) Breast cancer. In: CancerEpidemiology and Prevention Schottenfeld D, Fraumeni Jr JF (eds).995 – 1012. New York: Oxford University PressCostanza MC, Salamun J, Lopez AD, Morabia A (2006) Gender differentialsin the evolution of cigarette smoking habits in a general European adultpopulation from 1993 – 2003. BMC Public Health 6: 130Francis B, Green M, Payne CD (1993) GLIM 4 the Statistical System forGeneralized Linear Interactive Modelling. Oxford: Oxford University PressInternational agency for research on cancer (IARC) (2002) CancerMondial.Available from URL: http://www-dep.iarc.fr/ [cited 2007]International Union against Cancer (UICC) (eds). (1992) TNM Classifica-tion of Malignant Tumours. Berlin: Springer VerlagLutz JM, Reith-Chatton J, Fioretta G, Cerny V, Bouchardy C (2000) Surveyson mammography frequency in Geneva. J Med Screen 7: 111 – 113Magnusson CM, Roddam AW, Pike MC, Chilvers C, Crossley B, Hermon C,McPherson K, Peto J, Vessey M, Beral V (2005) Body fatness and physicalactivity at young ages and the risk of breast cancer in premenopausalwomen. Br J Cancer 93: 817 – 824Michels KB, Terry KL, Willett WC (2006) Longitudinal study on the role ofbody size in premenopausal breast cancer. Arch Intern Med 166: 2395 –2402Miller MD, Marty MA, Broadwin R, Johnson KC, Salmon AG, Winder B,Steinmaus C (2007) The association between exposure to environmentaltobacco smoke and breast cancer: A review by the CaliforniaEnvironmental Protection Agency. Prev Med 44(2): 93 – 106Morabia A, Costanza MC (2005) The obesity epidemic as harbinger of ametabolic disorder epidemic: trends in overweight, hypercholesterole-mia, and diabetes treatment in Geneva, Switzerland, 1993 – 2003. Am JPublic Health 95: 632 – 635National Cancer Institute (NCI) 2004 Surveillance, Epidemiology and EndResults SEER. Available from: URL: http://www.seer.cancer.gov/ [cited2007]World Health Organization (WHO) (1976) ICD-O International Classifica-tion of Diseases for Oncology. Geneva: World Health OrganizationYankaskas BC (2005) Epidemiology of breast cancer in young women.Breast Dis 23: 3 – 8Breast cancer in young womenC Bouchardy et al1746British Journal of Cancer (2007) 96(11), 1743 – 1746 & 2007 Cancer Research UKEpidemiology

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Recent increase of breast cancer incidence among women under the age of forty

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