an overview of prognostic factors for long-term survivors of breast cancer

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REVIEW

An overview of prognostic factors for long-term survivorsof breast cancer

Isabelle Soerjomataram Marieke W. J. LouwmanJacques G. Ribot Jan A. RoukemaJan Willem W. Coebergh

Received: 16 February 2007 / Accepted: 20 February 2007 / Published online: 22 March 2007Ó Springer Science+Business Media B.V. 2007

Abstract Background Numerous studies have examined prognosticfactors for survival of breast cancer patients, but relativelyfew have dealt specically with 10+-year survivors. Methods A review of the PubMed database from 1995 to2006 was undertaken with the following inclusion criteria:median/mean follow-up time at least 10 years; overallsurvival and/or disease-specic survival known; and rela-tive risk and statistical probability values reported. Inaddition, we used data from the long-standing EindhovenCancer Registry to illustrate survival probability as indi-cated by various prognostic factors. Results 10-year breast cancer survivors showed 90% 5-year relative survival. Tumor size, nodal status and graderemained the most important prognostic factors for long-term survival, although their role decreased over time.Most studies agreed on the long-term prognostic values of MI (mitotic index), LVI (lymphovascular invasion), Her2-positivity, gene proling and comorbidity for either all or a

subgroup of breast cancer patients (node-positive or neg-ative). The roles of age, socioeconomic status, histologicaltype, BRCA and p53 mutation were mixed, oftendecreasing after correction for stronger prognosticators,thus limiting their clinical value. Local and regionalrecurrence, metastases and second cancer may substantiallyimpair long-term survival. Healthy lifestyle was consis-tently related to lower overall mortality.Conclusions Effects of traditional prognostic factorspersist in the long term and more recent factors need fur-ther follow-up. The prognosis for breast cancer patientswho have survived at least 10 years is favourable and in-creases over time. Improved long-term survival can beachieved by earlier detection, more effective moderntherapy and healthier lifestyle.

Keywords Breast cancer ÁLong-term ÁPrognostic factors ÁSurvival

Introduction

Breast cancer (BC) is the most common cancer amongwomen, with a lifetime risk of up to 12% and a risk of death of up to 5% [ 1]. Its incidence has been increasing butafter a period of continuous rise in many industrializedcountries BC mortality has been stable or has even de-creased in the last 10–15 years [ 2, 3]. The introduction of mass mammographic screening programmes also resultedin earlier detection and diagnosis of small and lessaggressive tumours. This, in combination with therapeuticimprovements, has led to a substantial increase in BCsurvivors over the last few decades (Fig. 1). A long-termsurvivor is commonly dened as a person who is still alive5 years after cancer diagnosis [ 4]. For BC, the relative

I. Soerjomataram ( & ) ÁJ. W. W. CoeberghDepartment of Public Health, Erasmus MC, P.O. Box 2040,Rotterdam 3000 CA, The Netherlandse-mail: [email protected]

I. Soerjomataram ÁM. W. J. Louwman ÁJ. W. W. CoeberghComprehensive Cancer Centre South, P.O. Box 231, 5600 AEEindhoven, The Netherlands

J. G. RibotDepartment of Radiotherapy Catharina Hospital, P.O. Box 1350,5602 ZA Eindhoven, The Netherlands

J. A. RoukemaDepartment of Surgery, St. Elisabeth Hospital, P.O. Box 90151,5000 LC Tilburg, The Netherlands

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Breast Cancer Res Treat (2008) 107:309–330DOI 10.1007/s10549-007-9556-1



becoming more common with increasing age [ 13]. Com-pared to those without comorbidity whose 5-year relativesurvival was 87%, those with diabetes mellitus or cardio-vascular disease represented 78% and 83% of the respec-tive survival estimates [ 13]. Patients with severecomorbidity exhibited a 2.7–3.4 higher risk of death in10 years compared to those without comorbidity [ 12, 14].

Period of diagnosis Access to care and treatment of BChas improved over time in most industrialized countries,which is reected in the higher long-term survival of BCcases across all age groups and the tumour characteristicsof those diagnosed more recently [ 15–18]. In Finland,relative survival 10 years after diagnosis among patientsyounger than 50 years increased from 49% for thosediagnosed in 1953–1959 to 68% for the 1983–1989 cohort[15]. Furthermore, 60% of node-positive BC patientsdiagnosed in 1978–1979 in Italy survived 10 years orlonger compared to the 50% probability 10-year survivalfor those diagnosed in 1968–1969 [ 17]. In addition, chan-ges in BC diagnosis, e.g. screening[ 19, 20] and betterstaging [ 17], may partly be responsible for the observedincrease in the proportion of survivors.

Time after diagnosis The longer a woman survives BCthe more the prognosis improves, illustrated by conditionalsurvival [ 16, 21]. Probably the subgroup of patients who

survived longer had less aggressive tumours due to a dif-ferent genetic make-up or better life-style. In Australia,79% of women with localized BC survived 10 years afterdiagnosis, yet among those still alive 5 years after diag-nosis 84% had a 10-year survival [ 16]. The respectivevalues for regional vs. advanced BC were 53% and 68%[16]. Unlike other cancers, relative conditional survivalremained stable below 100% after 12 years of survival anddecreased again after about 19 years (Fig. 3) [5]. This maybe a consequence of late recurrences and metastases,second cancers or late side-effects of treatment [ 23].

Socioeconomic status (SES) and race A population-basedstudy of BC patients diagnosed in 1968–1999 in Franceshowed a diminishing role of SES on excess mortalityamong women with BC over these periods [ 24]. Long-termfollow-up studies reported that women with BC from lowsocial classes had a 20–50% poorer survival compared topatients from higher social classes [ 25, 26], although otherscontradicted this [ 27]. Low SES patients were more likelyto be diagnosed at a later stage, had more aggressive tu-mour characteristics and might have received sub-optimaltreatment. However, differences in these prognostic factorsdid not fully explain the variation in survival according tosocial class [ 25]. This is also the case when breast cancersurvival is studied according to race/ethnicity. Ten yearsafter treatment 58% of African Americans were still alivecompared to 66% of the white Americans. After adjustingfor other prognostic factors, 41% excess mortality from allcauses was still observed among African Americans com-pared to caucasians [ 28]. This suggests other residual fac-tors such as lifestyle (higher body weight was observedamong African Americans), comorbidity [ 14], genetics orvariation in the delivery of treatment, which inuenceoutcome beyond variation in tumour aggressiveness [ 29].

Fig. 2 Relative survival of breast cancer patients (n: 13,279)diagnosed in 1990–2002 and followed until 2004, according to ageat diagnosis in southeastern Netherlands

Fig. 3 Conditional 5-year relative survival (calculated using periodanalysis [ 22] of breast cancer patients diagnosed in southernNetherlands in 1985–2002 and followed until 2004, according toage. ( Dashed line ): diagnosed at 25–49 years, ( solid line ): diagnosedat 50–74 years

Breast Cancer Res Treat (2008) 107:309–330 311

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Tumour-related characteristics

Tumour size Tumour size is one of the strongest prog-nostic indicators (Fig. 4) [7, 30], even after 20 years of follow-up [ 8, 31]. A larger tumour has been related to morepositive lymph nodes [ 32], thus their interaction furtherinuences the survival from BC. Nonetheless, the inde-

pendence of survival by node status is shown by the lower10-year overall survival rate found for node-negative pa-tients with a tumour of 2–5 cm compared to those with atumour smaller than 1 cm, 66% vs. 79%, respectively [ 33].

Histological type The prognostic value of histologicaltype can be grouped into four: excellent, good, poor andvery poor prognosis [ 34]. BC with an excellent prognosis,such as invasive cribriform, tubular [ 35], tubulo-lobularand mucinous [ 36, 37] showed >80% survival at 10 years[9]. Tubular mixed, mixed ductal with special type, atyp-

ical medullary [ 38] and alveolar lobular carcinoma have agood prognosis with a 60–80% 10-year survival. Thosewith invasive papillary, classic lobular and medullarycancers have a worse prognosis. Finally, 10-year survivalamong those with ductal, solid lobular, mixed ductal andlobular carcinoma is below 50% [ 34]. In most populationsinltrating ductal carcinoma covers about 70% of alldiagnoses [ 36, 39]. Inammatory BC has a particularlypoor prognosis: about 30% survived 10 years [ 40].

Histological grade The most widely used grading sys-

tems are Scarff-Bloom-Richardson classication, Fishergrading nuclear system and Nottingham Combined Histo-logic Grade (NCHG) [ 41]. The validity of grading has beensubjected to inter-observer reproducibility and subjectivity

[42]. However, higher grades have been quite consistentlyassociated with lower long-term survival [ 7, 8, 31, 43–45].Depending on other prognostic factors, such as nodal statusor tumour size [ 46, 47], cumulative survival among pa-tients with the lowest score was 90–94% 10 years afterdiagnosis and 30–78% among those with the highest score[37, 48].

Regional lymph node involvement Lymph node involve-ment is a valuable indicator of long-term survival (Fig. 5)[8, 32]. Node- positive patients have about a 4–8 timeshigher mortality than those without nodal involvement[8, 9, 49]. The more nodes involved the worse the prog-nosis. Prognosis for patients with 10 or more involvedaxillary nodes showed 70% more deaths at 10 years thanfor those with 1–3 involved nodes [ 32]. The survival of node-positive patients improved due to better staging pro-cedures and application of systemic treatment [ 7, 31, 50].

Lymphovascular invasion (LVI) and molecular markers of tumours angiogenesis At the St. Gallen meeting in 2005,LVI was added to the prognostics for node-negative pa-tients [ 51]. Compared to patients having no LVI, a 60%higher BC mortality was observed for node-negative BCpatients having positive LVI [ 52, 53], although others didnot observe the independent role of LVI [ 46, 50]. In thisline of research, studies have also focused on the value of microvessel density [ 44], blood invasion (BVI) [ 54] andmarkers of angiogenesis (VEGFR (vascular endothelial

growth factor receptor), CD105, Tie-2) [ 55, 56] in pre-dicting long-term survival of BC patients, although theresults are still conicting.

Fig. 4 Cumulative survival proportion of breast cancer patientsdiagnosed in southern Netherlands in 1970–1994 and followed until2004, according to tumor size (based on pathological diagnosis). n

tumor size: <2 cm (n: 3263) • tumor size: 2–5 cm (n: 3420) m tumorsize: >5 cm (n: 474) x tumor size: involvement of skin (n: 1133) andunknown/not applicable tumor size: 1410

Fig. 5 Cumulative survival proportion of breast cancer patientsdiagnosed in southern Netherlands in 1970–1994 and followed until2004, according to nodal status (based on pathological diagnosis). n

node negative (n: 4452) • node status: 1–3 positive nodes (n: 3266) m

node status: 4–9 positive nodes (n: 255) x node status: 10+ positivenodes (n: 189), unknown/not applicable node status: 1538

312 Breast Cancer Res Treat (2008) 107:309–330

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Grouped prognostic factors Some of the prognosticfactors have been combined into a prognostic index, suchas the TNM classication and also the more current Not-tingham Prognostic Index (NPI), both highly predictive forestimating long-term survival [ 41]. TNM staging consistsof information on primary tumour size, involvement of theregional lymph node and the presence of distant metastasis.

Only 53% of patients with regional or locally advanced BChad survived 10 years after diagnosis compared to 79% of those with localised BC [ 16]. Patients with metastasis(stage: M1) at diagnosis exhibited very poor 10-yearsurvival (3.4%) [ 57].

Tumour size, grade and lymph node status make up theNPI [ 11 , 46, 49]. In a large series of 2879 BC patients,10-year survival proportion was 85% for those with thelowest NPI score and 19% for those with the highest score[11 ].

Recurrence, metastasis and second cancer

Patients with recurrent, metastasized or second cancergenerally exhibited lower long-term survival than thosewithout [ 9, 21, 58–61]. Ten years after surgery, the prob-ability for survival for another 10 years, thus 20 years afterdiagnosis, for node-negative patients aged ‡ 45 years, tu-mour £ 1 cm, grade 1 and without a recurrence or metas-tasis was 0.89. If a recurrence occurred, the probability of being alive at 20 years dropped to 0.72. If a metastasis wasobserved the probability of survival was only 0.18 [ 21].The prognosis decreases with larger primary tumour size,nodal involvement [ 62], higher grade,[ 21] early recurrence(within 5 years of surgery)[ 63], location of recurrence(regional rather than local ipsilateral) [ 59] and inadequateprimary cancer treatment [ 9, 64]. In the dataset of the ECR,overall survival was better for women without secondprimary tumours than for women who developed a newprimary cancer (Fig. 6). Only 68% of early BC patientswith second malignancies had survived 10 years of follow-

up compared to 78% of those without multiple cancers[65]. Younger BC patients are reported to have poorersurvival and a higher risk of second cancer [ 59]. Correctedfor race and grade, women in the 20-29 year old categorywho had a second BC had a probability of 10-year survivalprobability of only 23% compared to 57% for those with-out multiple cancers.

Other tumour markers

Hormone receptors The presence of hormone receptorssuch as oestrogen (ER) and progesterone (PR) receptorspredicts the long-term outcome of hormonal therapy [ 66],thus they have been more commonly used as a predictivemarker rather than as a prognostic marker. Thus given aparticular treatment, e.g. tamoxifen, ER-positive patientshave a considerably better prognosis than ER-negativepatients. The prognostic value is weak [ 30, 43] or negli-

gible [ 37], particularly in the early years after diagnosis[67].

HER-2 expression Node-positive patients with BC cellsshowing amplication of the gene for human epidermalgrowth factor receptor type 2 (HER2), and/or overexpres-sion of its product had a lower 10-year overall survivalproportion, 50% versus 65% for those without HER2amplication [ 17, 68]. After 10 years the difference insurvival persisted, although it became somewhat smal-ler[ 17]. Tumours that overexpress HER2 are more likely tocontain p53 abnormalities, to be hormone receptor- andbcl-2-negative and to have lymphoid inltration and a highmitotic index, all known to be markers of poor prognosisfor BC [ 17, 69, 70]. As for patients with node- negativetumours, HER2 did not seem to affect long-term survivalsignicantly [ 17, 37, 69]. HER-2 expression has beenvaluable in predicting treatment responses to trastuzumab,certain endocrine therapies and chemotherapy, adding toit’s role as a predictive marker [ 68].

Mitotic Activity Index (MAI) MAI is an indicator of tu-mour proliferative activity that represents the mitoticactivity in a given area of the tumour. Combined withanother prognostic factor (NCHG), MAI has proven to bean accurate tool for assessment of long-term survival [ 48].In a population-based study women with node-negativetumours <5 cm and a MAI ‡ 10 exhibited 80% survival at10 years compared to 90% for an MAI <10 [ 71].

Gene expression prole A very promising new nding isthe microarrays method, in which a set of intrinsic genes is

Fig. 6 Cumulative survival of breast cancer patients diagnosed insouthern Netherlands in 1970–1994 and followed-up until 2004,according to second cancer. Follow-up for patients with secondcancer begins at the date of second cancer diagnosis. n no secondcancer (n: 8137) • second breast cancer (n: 744) m second non-breastcancer (n: 819)


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clustered and segregated into major subgroups; BC with agood and poor prognosis prole is correlated to the prob-ability of distant metastases [ 72] or a tumour with basal orluminal characteristics which are strongly associated withER status [ 73]. In a study of 295 patients diagnosed withstage I or II breast cancer, those classied as having a goodprognosis prole had a 95% overall 10-year survival ratecompared to 55% for those with a poor prole [ 74]. Thisclassication predicted outcome regardless of the nodalstatus, implying that more accurate criteria have becomeavailable for administering adjuvant systemic treatment.

Various molecular markers BRCA1 & 2 mutations wererst identied in 1994 and are BC risk factors for somespecic groups [ 75]. Their role as prognostic indicator forlong-term (more than 10-year) survival has not yet beenestablished. A study of 496 women (median follow-up:116 months), 56 of whom (11%) carried a BRCA1/BRCA2

mutation, showed worse BC-specic survival for womenwith BRCA1 mutations than for those without (62% at10 years versus 86%; P < 0.0001), but not for women withthe BRCA2 mutation [ 76]. However, another study whichcompared patients from BRCA1, BRCA2 and non-BRCA1/2 families as well as sporadic cases did not con-rm the prognostic role of BRCA1/2 [ 77].

Long-term follow-up studies have not demonstrated anindependent effect of p53 mutations on long-term survival.The P53 mutation was related to a poor clinical prole forpatients, hence in multivariate analysis its role on survivaldiminished [ 10, 69, 78, 79].

A high level of tissue urokinase-type plasminogenactivator (uPA) and its inhibitors has been correlated withpoor outcome for node-negative and node-positive patients.Those having the highest level of uPA have a ve timesgreater risk of dying from BC compared to those with thelowest level [ 69]. Other factors such as Ki67 (MIB-1),cathepsin-D, DNA ploidy and S-phase have been suggestedas prognosticators of survival, with conicting results,particularly among long-term survivors. Their use in gen-eral clinical settings is therefore not recommended [ 80, 81].

Miscellaneous

Lifestyle Generally, increased death rates due to BC(13–20%), other causes (49–86%) and all causes(14–70%) have been observed among obese patients[82–85]. Normal body weight tended be more benecialin death from other causes than from BC: [ 83, 84] 9.5%of obese patients died from non-BC causes compared to6.4% and 5.8%, respectively, of the normal or interme-diate groups [ 82]. Obesity was also related to a 2-foldincreased risk of postmenopausal contralateral BC and a

60% higher occurrence of second other cancers [ 84].Therefore, normal weight may reduce the risk of secondpost-menopausal BC, second other cancers and overallmortality [ 83, 84, 86].

Compared with women who engaged in less than 9metabolic equivalent task (MET)-hours per week of activity, women who engaged in 9 or more MET-hours perweek had a 40% lower risk of death from all causes,translating into a 6% absolute (unadjusted) reduction inmortality [ 87], which emphasizes the need to advisephysical activity.

So far, although studies have not convincingly shownthe positive inuence of eating fruit, vegetables and soybean on long-term BC survival [ 85, 88], diets high in fruits,vegetables, legumes, poultry, and sh and a low intake of red meat, desserts and high fat dairy products are likely toprotect against mortality from non-BC causes [ 89].

Modication of BC’s prognostic factors

Various studies have questioned the role of BC risk factorsin determining the biological tumour features as mentionedabove. Indeed, BC risk factors seem to differ according tohistological type, grade, size, nodal status and ER/PRreceptor status [ 90–93]. For example, excessive alcoholintake and obesity increased the risk for the development of ER-positive tumours [ 92, 93]. As for late age at rst full-term birth and obesity are related to an increased risk of large tumours [ 91]. Hence, risk factors for BC may alsoaffect breast biology and clinical behaviour, thus also BC

prognosis.

Changing importance of prognostic factors over timeafter diagnosis

Commonly, the value of prognostic factors decreasesdepending on the length of the follow-up period [ 31, 94].Survival curves according to prognostic factors usuallyshow a large drop in survival for all stages during the rst5 years; afterwards the curve stabilizes. Studies agreed onthe long-lasting inuence of tumour size at diagnosis onsurvival, albeit attenuating over time [ 31, 94, 95]. Grade,nodal status and metastases were also valuable in predict-ing survival up to 20 years after diagnosis [ 31, 95]. Al-though, others have reported that 10 years after diagnosisonly tumour size [ 94] or nodal status [ 8] or old age [ 8]remained as an independent predictor of long-term sur-vival. Similarly, ER/PR status and MAI only had a sig-nicant prognostic role in the rst 5–10 years afterdiagnosis [ 67, 71, 96]. Because even 10 years after BCdiagnosis the probability of survival for BC patients doesnot seem to reach that of the general population, the role of


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T a

b l e 1

O v e r v i e w o f s t u d i e s r e p o r t i n g l o n g - t e r m p r o g n o s t i c f a c t o r s f o r b r e a s t c a n c e r ( B C ) p a t i e n t s

N o . A u t h o r , y e a r

N o . o f p a t i e n t s

M e a n / m e d i a n

f o l l o w - u p

( y r s ) U n i v a r i a t e

( U V ) a n a l y s i s s i g n i c a n t

M u l t i v a r i a t e


N o t s i g n i c a n t

R e m a r k s

1

H a e r s l e v a n d J a c o b s e n

1 9 9 5 [ 7 0 ] a

4 9 0

1 0 . 6

M S , T , N

, H t y p ,

M I , G

, P R , H

e r 2

A l l p a t i e n t s : N & P R

I n N + : M I & P R

I n N - : M

S & G

H e r 2

O v e r a l l s u r v i v a l w a s m e a s u r e d .

P 5 3 w a s r e l a t e d t o a b s e n c e o f

t u b u l a r f o r m a t i o n , h i g h G

,

E R - n e g a t i v e , h i g h P C N A

( p r o l i f e r a t i n g c e l l n u c l e a r

a n t i g e n ) s c o r e

2

P i e t i l a i n e n 1 9 9 5 [ 1 0 ]

3 9 2

1 1 . 1

P 5 3 , N

, T , H t y p , t u b u l a r

f o r m a t i o n , i n t r a d u c t a l

g r o w t h ,

m a r g i n f o r m a t i o n ,

n e c r o s i s , D N A p l o i d y ,

S - p h a s e f r a c t i o n

A l l p a t i e n t s : N , T , M I

I n N + : T , M I

I n N – : T , p 5 3 , G


P 5 3 i s r e l a t e d t o y o u n g e r a g e ,

M I , A I , G

, n u c l e a r

p l e o m o r p h i s m

3

H a e r s l e v 1 9 9 5 [ 7 9 ] a

4 9 0

1 1

P C N A

T , G

, P R

H e r 2 & P C N A

( P r o l i f e r a t i n g

c e l l n u c l e a r

a n t i g e n )


P R w a s o n l y a n i n d e p e n d e n t

f a c t o r i n N - p o s i t i v e p t s . H e r 2

& P C N A w e r e r e l a t e d t o m o r e

p o s i t i v e N

, h i g h e r G , E R - / P R -

n e g a t i v e

4

G a m e l 1 9 9 6 [ 3 9 ]

1 6 3 , 8 0 8

N R

. R a n g e

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H i s t o l o g i c a l t y p e

b y s t a g e ( l o c a l i z e d &

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B r e a s t c a n c e r s p e c i c s u r v i v a l

w a s m e a s u r e d

5

W e s t 1 9 9 6 [ 1 2 ]

1 1 9 6

N R

. D i a g n o s e d :

1 9 7 3 – 1 9 8 6 .

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o m o r b i d i t y

L e v e l o f c o m o r b i d i t y

A d j u s t e d f o r a g e ,

r a c e , s t a g e ,

N , t h e r a p y .

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f a c t o r s w e r e n o t

s h o w n


C h a r l s o n c o m o r b i d i t y i n d e x

w a s u s e d . T h e r e i s n o

d i f f e r e n c e i n t h e s i g n i c a n c e

o f c o m o r b i d i t y o n s u r v i v a l o f

C a u c a s i a n s a n d A f r i c a n

A m e r i c a n ( A A )

6

H a e r s l e v 1 9 9 6 [ 1 1 2 ] a

4 8 7

> 1 0

K i - 6 7 , P C N A

T , G

, P R

K i - 6 7 & P C N A

.


P R o n l y a n i n d e p e n d e n t f a c t o r

f o r N + p a t i e n t s . K i - 6 7 w a s

r e l a t e d t o T , M I , G

7

N o r t h r i d g e 1 9 9 7 [ 3 6 ]

M u c i n o u s B C : 4 0 8 2 .

I n l t r a t i n g d u c t B C :

1 3 9 , 1 5 4

N R


1 9 7 3 – 1 9 9 0

H T y p , p e r i o d o f d i a g n o s i s ,

S t a g e , G

A g e



8

K o l l i a s 1 9 9 7 [ 1 1 ] a

2 8 7 9 a g e £ 7 0 , T < 5 c m

> 1 0

A g e < 3 5 , N P I

T , G

, N

A g e


Y o u n g e r t h a n 3 5 y r s h a d

h i g h e r g r a d e , m o r e L V I a n d

w o r s e N P I g r o u p . A f t e r 1 0 y r s

N P I d i d n o t c h a n g e O S


123



T a

b l e 1 c o n t i n u e d




f o l l o w - u p






R e m a r k s

9

Z a h l a n d T r e t l i 1 9 9 7

[ 9 5 ]

8 8 0 2 a g e < 7 0

D i a g n o s e d :

1 9 6 5 – 7 4 . E n d

F U : 1 9 9 1

S u r v i v a l

c a t e g o r i z e d b y a g e ,

s t a g e a n d

f o l l o w - u p t i m e

E x c e s s h a z a r d f r o m b r e a s t

c a n c e r w a s m e a s u r e d . A f t e r

8 y r s

b e i n g y o u n g e r t h a n

3 5 d o e s n o t i n u e n c e

s u r v i v a l . S t a g e w a s a n

i m p o r t a n t p r o g n o s t i c a t o r u p t o

2 0 y r s

1 0

P i n d e r 1 9 9 8 [ 4 7 ]

4 6 5

1 2

N b y g r a d e ,

T r e a t m e n t b y g r a d e


T h e s t u d y a i m e d t o c o n r m

v a l u e o f N o t t i n g h a m g r a d i n g

s y s t e m f o r s u r v i v a l . N + G 3

p a t i e n t s b e n e t e d f r o m

p r o l o n g e d c h e m o t h e r a p y

1 1

G a f f n e y 1 9 9 8 [ 1 1 3 ]

B R C A 1 : 3 0

B R C A 2 : 2 0

C o n t r o l : 1 8 2 7 8

B C p t s

B R C A 1 : 9 . 8

B R C A 2 : 7 . 5

C o n t r o l : N R

B R C A 1 v s . B R C A 2

v s . c o n t r o l

O v e r a l l s u r v i v a l w a s m e a s u r e d

C a s e a n d c o n t r o l w e r e m a t c h e d

f o r d a t e o f b i r t h , d a t e o f

d i a g n o s i s a n d t u m o u r s i z e .

P a t i e n t s w i t h B R C A + w e r e

y o u n g e r . P a t i e n t s w i t h B R C A 1

h a d h i g h e r g r a d e

1 2

W o j c i k 1 9 9 8 [ 2 8 ]

6 5 7 7 p a t i e n t s

W h i t e s : 5 8 7 9

A f r i c a n A m e r i c a n ( A A ) :

6 9 8

A t 1 0 y r s 5 9 –

6 7 % p a t i e n t s

w e r e a l i v e

R a c e , G

, N , T ,

s t a g e ,

w a i t i n g t i m e ,

s m o k i n g , b e i n g a w i d o w

,

h a v i n g

o t h e r f a m i l y a s

d e p e n d e n t

R a c e , a g e , s t a g e

U V : a l c o h o l , f a m i l y

h i s t o r y


A A i s m o r e l i k e l y t o b e

y o u n g e r a t d i a g n o s i s , h a v e

l a r g e r t u m o u r , h i g h e r s t a g e

a n d m o r e l y m p h n o d e s

1 3

M a n s i 1 9 9 9 [ 1 1 4 ]

3 5 0

1 2 . 5

B o n e m a r r o w

m i c r o m e t a s t a s e s

N , T

B o n e m a r r o w

m i c r o m e t a s t a s e s ,

L V I

O v e r a l l a n d b r e a s t c a n c e r -

s p e c i c s u r v i v a l w a s

m e a s u r e d . B o n e m a r r o w

m e t a s t a s e s m a y b e u s e f u l a s

p r o g n o s t i c f a c t o r f o r B C p t s

w i t h o u t i n f o r m a t i o n o n T a n d

N

1 4

K o l l i a s 1 9 9 9 [ 4 6 ] a

3 1 9 T £ 1 c m

> 1 0

G , N , L V

I , N P I

G , N

L V I


1 5

T a b a r 1 9 9 9 [ 4 5 ]

2 4 6 8

N R


1 9 7 7 – 8 5 . E n d

F U : 1 9 9 6

T , N

, G , d e t e c t i o n

m o d e , H T y p

T X N

, a g e * N , H

t y p * N ,

T * N * G


S c r e e n i n g a r r e s t s d i s e a s e

p r o g r e s s i o n . T u m o u r

p r o g r e s s i o n i s m o r e r a p i d i n

B C p a t i e n t s < 5 0 y r s . O S o f

T 1 a ( 1 – 5 m m ) v s .

T 1 b ( 6 – 1 0 m m ) N S .


123



T a





f o l l o w - u p






R e m a r k s

1 6

H o l m e s 1 9 9 9 [ 8 5 ]

1 9 8 2

1 3 . 1

B M I ‡ 3 0

3 r d t o 5 t h q u i n t i l e

o f p r o t e i n p r o t e i n

i n t a k e a f t e r

d i a g n o s i s , N , T , G

B M I , p r o t e i n i n t a k e

p r i o r d i a g n o s i s , a l c o h o l

i n t a k e

A l l c a u s e m o r t a l i t y w a s

m e a s u r e d . M V f o r B M I w a s

c o r r e c t e d f o r a g e , d i e t

i n t e r v a l , o r a l c o n t r a c e p t i v e

u s e , h o r m o n e r e p l a c e m e n t

t h e r a p y , M S , a g e a t m e n a r c h e ,

a g e t a t b i r t h a n d p a r i t y ,

s m o k i n g , T , G

, N , E R , P R

B M I < 2 1 a n d 1 s t q u i n t i l e o f

p r o t e i n i n t a k e w e r e r e f e r e n c e .

S i g n i c a n t t r e n d o f h i g h e r

m o r t a l i t y f r o m l o w e s t t o

h i g h e s t q u i n t i l e s o f b r e ,

l u t e i n a n d z e a x a n t h i n ,

c a l c i u m a n d p r o t e i n i n t a k e ,

w i t h 1 3 – 3 5 % l o w e s t m o r t a l i t y

i n t h e l o w e s t q u i n t i l e

1 7

N o m u r a 1 9 9 9 [ 5 8 ]

1 8 5 7 < 8 0 y r s

s t a g e I - I I I

1 2

S e c o n d c a n c e r

a n d r e c u r r e n c e

A g e , E R

, N , r e c

u r r e n c e ,

s e c o n d c a n c e r


R e c u r r e n c e i s r e l a t e d t o h i g h e r

s t a g e , y o u n g e r a g e

a t

d i a g n o s i s , H t y p , a n d t h e r a p y .

S e c o n d c a n c e r i s r e l a t e d t o

y o u n g e r a g e . D e a t h r e l a t e d t o

r e c u r r e n c e a n d s e c o n d c a n c e r

i s i n c r e a s e d 1 2 y r s a f t e r

d i a g n o s i s .

1 8

R e e d 1 9 9 9 [ 3 7 ]

6 1 3 T 1 - 2 N 0

1 5 . 5

A g e > 5 0 , T , G

G , T ,

t r e a t m e n t

U V : t r e a t m e n t , E R

,

P R , H

e r 2 , P 5 3


H e r 2

w a s r e l a t e d t o P R - ,

E R -

n e g a t i v e , P 5 3 , G

. P 5 3 w a s

r e l a t e d t o P R - .

T r e a t m e n t w a s

o v a r i a n & l o c o r e g i o n a l

i r r a d i a t i o n t h a t h a d l o w e r

m o r t a l i t y r a t e

1 9

A e b i 2 0 0 0 [ 7 ]

3 7 0 0 p r e - &

p e r i m e n o p a u s a l

1 2

A g e < 3 5 v s . ‡ 3 5

N , T ,

G , a g e < 3

5 * E R +

A g e , E R


Y o u n g e r p a t i e n t s w i t h E R +

w h o w e r e n o t a m e n o r r h o e a

h a d a s i g n i c a n t l y s h o r t e r

s u r v i v a l

2 0

F e r r e r o 2 0 0 0 [ 7 8 ]

2 9 7 N -

1 1

T , E R

, P 5 3

T , E R

A g e , P R

, G

B r e a s t c a n c e r - s p e c i c s u r v i v a l

w a s m e a s u r e d . P 5 3 w a s

r e l a t e d t o g r a d e , T , E R -

n e g a t i v e . P 5 3 w a s c o n t i n u o u s

v a r i a b l e


123



T a





f o l l o w - u p






R e m a r k s

2 1

K r o m a n 2 0 0 0 [ 6 ]

1 0 , 3 5 6 a g e < 5 0

N R


1 9 7 8 – 9 6 .

A g e , T , N

, G

P e r i o d o f t r e a t m e n t

a n d s u r g e r y

R e l a t i v e s u r v i v a l w a s m e a s u r e d

f o r e x c e s s m o r t a l i t y d u e t o

B C . W h e n c h e m o t h e r a p y w a s

g i v e n B C a t y o u n g a g e d o e s

h a v e w o r s e p r o g n o s i s

2 2

F e r r e r o - P o u s 2 0 0 0 [ 6 9 ] 4 8 8

1 0

E R , u P A , G , N , P R , P 5 3

b y

H e r 2

A l l p a t i e n t s : u P A

, N , T ,

H e r 2 , a g e

I n N – : u P A , T

I n N + : N : u P A , T , a g e ,

H e r 2


F o r p a t i e n t s w h o r e c e i v e d

c h e m o t h e r a p y u P A , T

& N

d e t e r m i n e d O S . F o r p a t i e n t s

w h o r e c e i v e d h o r m o n a l

t h e r a p y u P A , H

e r 2 & N

d e t e r m i n e d O S

2 3

K a t o 2 0 0 1 [ 4 4 ] a

3 7 7

1 0

T , N

, G

A M C

, T , N

, G

N e c r o s i s


A M C

i s a g o o d p r o g n o s t i c

f a c t o r f o r N - a n d T 2 - 3

p a t i e n t s

2 4

L i u 2 0 0 1 [ 9 6 ]

7 9 1

1 6 . 3

T , N

, G , E R , H

e r 2 , p 5 3 ,

M I B - 1 , M

A I , A I

A l l p a t i e n t s : N , T , G

, E R ,

H e r - 2

I n N – : G

I n N + : N , a g e ,

E R , H

e r 2

U V : a g e . M V A l l

p a t i e n t s : A I , M I ,

M I B - 1 , E R , G

M V i n N -

& N + :

A I , M I , E R

, G .

B r e a s t c a n c e r - s p e c i c m o r t a l i t y

w a s m e a s u r e d . W h e n p a t i e n t

F U w a s t r u n c a t e d a t 5 y r s , M I

w a s p r o g n o s t i c f a c t o r f o r N +

a n d N -

2 5

P a g e 2 0 0 1 [ 1 1 5 ]

3 1 1 n o a d j u v a n t

t h e r a p y .

1 1 . 6

H i g h r i s k g r o u p ( E R - o r

T ‡ 3 c m ) v s .

l o w r i s k ( E R + a n d T

< 2 c m )

T , r i s k g r o u p

( h i g h v s . l o w )

G , M

I


M I w a s o n l y s i g n i c a n t w h e n

F U w

a s t r u n c a t e d a t 5 y r s .

G r a d e w a s s i g n i c a n t

p r o g n o s t i c f a c t o r f o r s h o r t -

a n d l o n g - t e r m s u r v i v a l .

2 6

F r k o v i c - G r a z i o a n d

B r a c k o 2 0 0 1 [ 4 8 ]

2 7 0 T 1 N 0 M 0

1 2 . 5

G , T u b u l a r

s c o r e , M I

T u b u l a r s c o r e a n d M I


w a s m e a s u r e d . T h i s s t u d y

c o n r m e d t h e u s e o f

N o t t i n g h a m g r a d i n g s y s t e m i n

t h e i r c o h o r t

2 7

D ’ E r e d i t a 2 0 0 1 [ 4 9 ]

4 0 2

‡ 1 6

T , N

, H t y p , G

, L V I , N P I

T , N

, G

U V : A g e , M S , E R

,

t y p e o f s u r g e r y

M V : L V I & H t y p


N P I g i v e s s i m i l a r s u r v i v a l

p r o g n o s i s a s T , N

, G

2 8

T h o m s o n 2 0 0 1 [ 2 6 ]

2 3 7 8 6

A t 1 0 y r s a b o u t

5 0 % p a t i e n t s

w e r e a l i v e

A g e s t r a t i e d b y S E S

I n t e r m e d i a t e v s . h i g h

S E S

g r o u p c o r r e c t e d f o r a g e ,

E R , N , T ,

s t a g e

D e p r i v e d v s . h i g h

S E S g r o u p

c o r r e c t e d f o r a g e ,

E R , N , T ,

s t a g e

D e p r i v e d w o m e n h a v e m o r e E R -

t u m o u r s . E R d i s t r i b u t i o n a n d

t r e a t m e n t m e t h o d a c c o u n t e d

f o r 2 0 % o f d i s p a r i t i e s i n

s u r v i v a l

2 9

V o r g i a s 2 0 0 1 [ 3 0 ]

2 6 9 s t a g e I I

1 2

N R

T , N

, a g e , E R / P R

M S , t h e r a p y



123



T a





f o l l o w - u p






R e m a r k s

3 0

V i n c e n t - S a l o m o n 2 0 0 1

[ 4 3 ]

6 8 5 T £ 3 c m

1 0 . 8

G , N , E R , n e c r o s i s

N , n e c r o s i s ,

G

U V : V a s c u l a r

d e n s i t y , L V I , a g e ,

P R


I n t r a t u m o r a l v a s c u l a r d e n s i t y

w a s r e l a t e d t o l a r g e r t u m o u r

s i z e a n d h i g h e r g r a d e

3 1

E e r o l a 2 0 0 1 [ 7 7 ]

F a m i l i a l B C : 3 5 9

S p o r a d i c B C : 5 9 5 1 7

N R

D i a g n o s e d :

1 9 5 3 – 1 9 9 5 E n d

F U : 1 9 9 7

S t a g e , a g e , p e r i o d o f B C

d i a g n o s i s , F U

t i m e ( a f t e r

2 a n d 3 y r s o f d i a g n o s i s )

B R C A 1 , B R C A 2

5 - y e a r r e l a t i v e s u r v i v a l w a s

m e a s u r e d f o r e x c e s s m o r t a l i t y

d u e t o B C

3 2

K i t c h e n 2 0 0 1 [ 3 5 ]

9 5 2 0

1 2

T u b u l a r B C t y p e v s . o t h e r

t y p e , b y n o d a l s t a t u s a n d

c h e m o t h e r a p y


T u b u l a r B C t y p e h a d b e t t e r

p r o g n o s i s t h a n o t h e r t y p e .

T h i s t y p e w a s m o r e l i k e l y t o

h a v e l o w G & E R +

3 3

K a t o 2 0 0 2 [ 5 0 ] a

4 2 2

1 0

P 5 3 , M I , n e c r o s i s , T , N

,

L V I

M I , T , N

U V : A I


I n M V P 5 3 & M I w e r e

i n d e p e n d e n t p r o g n o s t i c f a c t o r s

f o r N - p a t i e n t s o n l y . P 5 3 w a s

r e l a t e d t o M I , A I , n e c r o s i s , G

, T ,

N , E R /

P R

3 4

K a t o 2 0 0 2 [ 5 4 ] a

3 9 8

1 0

B V I , T , N

, G ,


B V I , T , N

, G ,


U V : n e c r o s i s


3 5

C o s t a 2 0 0 2 [ 6 7 ]

6 7 0

1 1 . 4

N , T ,

a g e , E R / P R

N , T ,

a g e

M S , E R / P R


w a s m e a s u r e d . A f t e r 5 y r s o f

F U E R a n d P R w e r e n o t

i n d e p e n d e n t p r o g n o s t i c

f a c t o r s

3 6

M e n a r d 2 0 0 2 [ 1 7 ]

1 9 2 8

D i a g n o s e d i n

1 9 6 8 – 6 9 a n d

1 9 7 8 – 7 9

H e r 2 , N , T ,

M S ,

l y m p h o i d i n l t r a t i o n ,

P R -

G , T ,

N , l y m

p h o i d

i n l t r a t i o n


H E R - 2 w a s r e l a t e d t o l a r g e

t u m o u r s , h i g h e r G

, l y m p h o i d

i n l t r a t i o n , h i g h e r m i t o t i c

i n d e x , P R -

3 7

V a n d e V i j v e r 2 0 0 2 [ 7 4 ] 2 9 5 a g e < 5 3 , s t a g e I - I I 6 . 7

G e n e p r o l e ( G o o d v s .

b a d p r o g n o s i s ) f o r a l l

p a t i e n t s , N + , N –

G e n e p r o l e , T , N ,


V I , G

, a g e , h o r m o n a l

t h e r a p y


3 8

V a n ’ t V e e r 2 0 0 2 [ 7 2 ]

1 1 7 a g e < 5 5

N R

B e t t e r c l a s s i c a t i o n o f p a t i e n t s

w i t h h i g h r i s k o f m e t a s t a s i s

a n d i n n e e d o f c h e m o t h e r a p y


123



T a





f o l l o w - u p






R e m a r k s

3 9

H a t t e v i l l e 2 0 0 2 [ 2 1 ]

3 1 8 0

1 5 . 8

O S < 5 y e a r : N , G

,

r e c u r r e n c e o r m e t a s t a s i s

O S ‡ 5 y r : G a n d

r e c u r r e n c e

o r m e t a s t a s i s

A g e , T

I f p a t i e n t r e m a i n s w i t h o u t

r e c u r r e n c e o r m e t a s t a s i s ,

e f f e c t o f p r o g n o s t i c f a c t o r s

d e c r e a s e s o v e r t i m e . W i t h

m e t a s t a s e s , t h i s e f f e c t

i n c r e a s e s

4 0

S o t i r i o u 2 0 0 3 [ 7 3 ]

9 9

6 . 1

G e n e p r o l e ( l u m i n a l 1 – 3

v s . b a s a l 1 – 2 & H e r 2

t y p e )

L u m i n a l - l i k e 1 – 3 w a s

p r e d o m i n a n t l y E R + . B a s a l -

l i k e 1 – 2 a n d H e r 2 w a s

p r e d o m i n a n t l y E R -

4 1

D i g n a m 2 0 0 3 [ 8 3 ]

3 3 8 5 N – ,

E R +

1 3 . 8

B M I < 1 8 . 5 a n d B M I ‡ 3 0

h i g h e r t o t a l m o r t a l i t y a n d

o t h e r d e a t h s .

B M I o n

d e a t h s a f t e r B C

e v e n t s .

T o t a l m o r t a l i t y , d e a t h a f t e r B C

e v e n t s a n d o t h e r d e a t h s a s

w e l l a s r e c u r r e n c e r a t e a n d

o c c u r r e n c e o f a s e c o n d c a n c e r

w a s w e r e m e a s u r e d . M V w a s

a d j u s t e d f o r t r e a t m e n t , a g e ,

M S , r a c e , T , E R a n d P R

.

R e f e r e n c e g r o u p w a s B M I

1 8 . 5 – 2 4 . 9 .

4 2

O l i v o t t o 2 0 0 3 [ 5 7 ]

6 2 0 s t a g e I I I B - M

1

> 2 0

S u p r a c l a v i c u l a r B C

,

S t a g e I I I B a n d M 1

O v e r a l l a n d b r e a s t c a n c e r

s p e c i c s u r v i v a l w e r e

m e a s u r e d . P a t i e n t s w i t h

s u p r a c l a v i c u l a r m e t a s t a s e s

h a d s i g n i c a n t l y b e t t e r

s u r v i v a l t h a n p a t i e n t s w i t h

M 1 . S u r v i v a l o f t h e s e p a t i e n t s

r e s e m

b l e s t h a t o f B C s t a g e

I I B . ( F U f o r l i v i n g p a t i e n t s 2 0

y r s , f o r a l l p a t i e n t s 4 . 5 y r s )

4 3

W e i s s 2 0 0 3 [ 3 2 ]

9 0 5 N +

C h e m o t h e r a p y +

2 2 . 6

N + ( N 1 – 3 v s . N 4 – 9 v s .

N > 1 0 ) , a l s o b y

t r e a t m e n t a n d

f o l l o w - u p t i m e

N , T ,

M S

M V : N X T , M S X T ,

a d d i t i o n a l

v i n c r i s t i n e a n d

p r e d n i s o n


N w a s r e l a t e d t o T . M S w a s

r e l a t e d t o r e c e p t o r s t a t u s

4 4

T a y l o r 2 0 0 3 [ 1 6 ]

5 4 , 2 2 8

A t 1 0 y r s 6 5 %

p a t i e n t s w e r e

a l i v e

P e r i o d o f d i a g n o s i s , s t a g e

b y a g e , F U t i m e b y s t a g e


f o r e x c e s s m o r t a l i t y d u e t o B C

T h e l o n g e r t h e s u r v i v a l t h e

b e t t e r t h e p r o g n o s i s .

I m p r o v e m e n t i n r e l a t i v e s u r v i v a l

f o r a l l p a t i e n t s a n d a l l s t a g e s

s i n c e 1 9 7 2


123



T a





f o l l o w - u p






R e m a r k s

4 5

D a l e s 2 0 0 4 [ 5 6 ]

9 0 5 a g e d 2 5 – 8 1

1 1 . 7

I n N - : C D 1 0 5 + v e s s e l s . I n

a l l p t s : C D 3 1 , T i e - 2 / T e k

I n a l l p t s : G , C

D 1 0 5

v e s s e l s , E R

I n N – : G , C

D 1 0 5 v e s s e l s ,

P R

I n a l l p t s : T , H t y p ,

C D 3 1 , P R

, a g e . I n

N – : T ,

C D 3 1

v e s s e l s , E R

, a g e


M V : T i e - 2 / T e k s h o w e d

s i g n i c a n t r o l e f o r p r e d i c t i n g

O S i n a l l p a t i e n t s a n d N -

p a t i e n t s

4 6

B r e n n e r a n d H a k u l i n e n

2 0 0 4 [ 1 5 ]

1 8 , 5 7 8 a g e < 5 0

N R


1 9 5 3 – 1 9 9 9 .

P e r i o d o f d i a g n o s i s ,

s t a g e , s t a g e * p e r i o d , t i m e

a f t e r d i a g n o s i s

I m p r o v e m e n t o f p r o g n o s i s f o r

B C p a t i e n t s y o u n g e r t h a n 5 0

o v e r t h e p a s t d e c a d e s .

R e l a t i v e s u r v i v a l r e m a i n s

l o w e r e d e v e n 4 0 y r s a f t e r

d i a g n o s i s

4 7

R o b s o n 2 0 0 4 [ 7 6 ]

5 8 4 A s h k e n a z i J e w i s h

1 1 6

B R C A 1 , T , N

, E R , a g e ,


B R C A 1 , T , N , A g e

T a m o k s i f e n ,

B R C A 2


w a s m e a s u r e d . N o e f f e c t o f

B R C A o n n o n - B C d e a t h .

B R C A 1 o n l y p r e d i c t e d B C

d e a t h

i n p a t i e n t s w i t h o u t


4 8

C h i a 2 0 0 4 [ 3 3 ]

1 1 8 7 L V I - , N - ,

A d j u v a n t s y s t e m i c

t h e r a p y -

1 0 . 4

T , G

T X G

O v e r a l l a n d b r e a s t c a n c e r

s p e c i c s u r v i v a l w e r e

m e a s u r e d . P a t i e n t s w i t h

h i g h e r g r a d e a n d s i z e h a v e

g r e a t e r c h a n c e t o d i e f r o m

o t h e r & t h o s e w i t h l o w r i s k

d i s e a s e g r e a t e r c h a n c e o f

d e a t h

f r o m B C

4 9

Y o s h i m o t o 2 0 0 4 [ 1 8 ]

1 5 , 4 1 6

N R

. D i a g n o s e d

1 9 4 6 – 2 0 0 1 .

P e r i o d o f d i a g n o s i s

O v e r t h e d e c a d e s , t h e r e w e r e

l e s s e x t e n s i v e s u r g e r y a n d

l y m p h n o d e e x a m i n a t i o n , l e s s

r a d i o t h e r a p y , m o r e c h e m o -

a n d h o r m o n a l t h e r a p y

5 0

H o u t e r m a n 2 0 0 4 [ 1 1 6 ] 5 2 7 a g e ‡ 4 0

4 . 7

C o m o r b i d i t y , N

, T h e r a p y ,

a g e ‡ 7 0 , c o m o r b i d i t y * N

I n a g e < 7 0 : c o m o r b i d i t y , N

I n a g e ‡ 7 0 : c o m o r b i d i t y ,

a g e

I n a g e < 7 0 : t h e r a p y

I n p t s a g e ‡ 7 0 : N

,

t h e r a p y



O l d e r p a t i e n t s w i t h c o m o r b i d i t y

w e r e n o t t r e a t e d d i f f e r e n t l y b u t

h a d a w o r s e p r o g n o s i s

5 1

S c h o p p m a n n 2 0 0 4 [ 5 3 ] 3 7 4

2 2 . 4

L V

I , G , N , T h e r a p y

L V I , G

, N

L M V D ( L y m p h a t i c

M i c r o v e s s e l

D e n s i t y ) , T , H t y p ,

E R , a g e ,

M S


L V I i s r e l a t e d t o y o u n g

p r e m e n o p a u s a l B C

, l o w e r G

,

N +


123



T a





f o l l o w - u p






R e m a r k s

5 2

W a r w i c k 2 0 0 4 [ 3 1 ]

2 2 9 9

> 1 0

G , N , T ,

M e t a s t a s e s

G , N , T ,

M e t a s t a s e s


w a s m e a s u r e d . A l l s t u d i e d

f a c t o r s p r e d i c t e d l o n g - t e r m

s u r v i v a l , b u t t h e i r v a l u e

d e c r e a s e d o v e r t i m e

5 3

B e r c l a z 2 0 0 4 [ 8 2 ]

6 7 9 2

1 4

B M

I 2 5 – 2 9 , B M I ‡ 3 0 l o w e r

o v e r a l l s u r v i v a l

B M I ‡ 3 0

B M I 2 5 – 2 9

O v e r a l l s u r v i v a l a n d a l s o d i s e a s e

f r e e s u r v i v a l w e r e m e a s u r e d .

R e f e r e n c e g r o u p w a s B M I £

2 4 . 9 . M

V a d j u s t e d f o r E R

, T ,

N , M

S , t r e a t m e n t ,

c h e m o t h e r a p y , h o r m o n a l - i n

c o m b i n a t i o n w i t h


5 4

D i g n a m 2 0 0 5 [ 8 4 ]

4 0 7 7 N - ,

E R -

N R

B M I ‡ 3 5 a n d A A h a d

h i g h e r o v e r a l l m o r t a l i t y

a n d n o n - B C d e a t h

B M I a n d r a c e o n

d e a t h a f t e r B C

e v e n t s

T o t a l m o r t a l i t y , d e a t h a f t e r B C

e v e n t s a n d o t h e r d e a t h s a s

w e l l a s r e c u r r e n c e r a t e a n d

o c c u r r e n c e o f a s e c o n d c a n c e r

w e r e m e a s u r e d . M V w a s

a d j u s t e d f o r t r e a t m e n t , a g e ,

M S , r a c e , T , E R a n d P R

R e f e r e n c e g r o u p w a s B M I £ 2 4 . 9

5 5

H o l m e s 2 0 0 5 [ 8 7 ]

2 9 8 7

9 6 m o n t h s

P h y s i c a l a c t i v i t y

a f t e r

d i a g n o s i s ( M E T ‡ 9 ) o n

B C a n d t o t a l m o r t a l i t y

B r e a s t c a n c e r a n d t o t a l m o r t a l i t y

w e r e m e a s u r e d . M V c o r r e c t e d

f o r a g e , i n t e r v a l b e t w e e n

d i a g n o s i s a n d p h y s i c a l

a c t i v i t y a s s e s s m e n t , s m o k i n g ,

B M I

, M S , h o r m o n e t h e r a p y

u s e , a g e a t r s t b i r t h , p a r i t y ,

e n e r g y i n t a k e , s t a g e a n d

t r e a t m e n t . M E T : m e t a b o l i c

e q u i v a l e n t t a s k h o u r s p e r

w e e k . P a t i e n t s

w i t h B M I ‡ 2 5

a n d m o r e p h y s i c a l a c t i v i t y

b e f o r e d i a g n o s i s t h e r e w a s a

s i g n i c a n t t r e n d f o r l e s s

b r e a s t c a n c e r d e a t h

5 6

R o b s a h m a n d T r e t l i

2 0 0 5 [ 2 7 ]

5 0 4 2

N R


1 9 6 4 – 9 2 . E n d

F U : 1 9 9 2

N R

L o c a t i o n o f h o m e , a g e a t

r s t c h i l d , p h y s i c a l

a c t i v i t y a t w o r k

M V c o r r e c t e d f o r :

a g e , p e r i o d o f

d i a g n o s i s , b i r t h

c o h o r t ,

e d u c a t i o n a l l e v e l B r e a s t c a n c e r - s p e c i c s u r v i v a l

w a s m e a s u r e d . I n c i d e n c e o f

B C i n c r e a s e s w i t h h i g h e r

e d u c a t i o n a l l e v e l , a n d c a s e

f a t a l i t y d e c r e a s e s b y

i n c r e a s i n g e d u c a t i o n l e v e l


123



T a





f o l l o w - u p






R e m a r k s

5 7

V u - N i s h i n o 2 0 0 5 [ 3 8 ]

1 4 9 0 r e c e i v e d b r e a s t -

c o n s e r v i n g t r e a t m e n t

1 3 . 9

M e d u l l a r y B C v s .

o t h e r B C t y p e


M e d u l l a r y B C t y p e h a d b e t t e r

p r o g n o s i s t h a n o t h e r t y p e .

T h i s t y p e w a s m o r e l i k e l y t o

h a v e E R + , P R + & l e s s

B R C A 1 / 2 m u t a t i o n .

M e d u l l a r y t y p e w a s o n l y a

p r o g n o s t i c f a c t o r f o r t h e r s t

5 y r s

5 8

G a l p e r 2 0 0 5 [ 6 3 ]

2 1 0 2 s t a g e I - I I , 3 1 4 w i t h

l o c a l r e c u r r e n c e ( L R )

1 3 . 1

N R

N o L R t r e a t m e n t , I n v a s i v e

L R , t i m

e ( y r s ) t o l o c a l

r e c u r r e n c e , a g e a t i n i t i a l

B C d i a g n o s i s

T , d e t e c t i o n m e t h o d ,

n u m b e r o f n o d e s

s a m p l e d , E R / P R

,

h i s t o l o g i c a l t y p e ,

G , L V

I , m a r g i n s

M e a s u r e o f s u r v i v a l : d i s t a n t

f a i l u r e , s e c o n d m a l i g n a n c y , o r

d e a t h

P a t i e n t s w i t h a l o n g e r t i m e t o

r e c u r r e n c e h a v e p r o l o n g e d

s u r v i v a l

5 9

V o o g d 2 0 0 5 [ 6 2 ]

2 6 6 B C w i t h L R

1 1 . 2 a f t e r L R f o r

l i v i n g p t s

N R

L o c a t i o n o f L R , s i z e o f L R ,

s k i n i n v o l v e m e n t o f L R

,

N + f o r p r i m a r y t u m o u r


E a r l y

d e t e c t i o n o f l o c a l

r e c u r r e n c e m a y i m p r o v e t h e

t r e a t m e n t o u t c o m e

6 0

L o u w m a n 2 0 0 5 [ 1 3 ]

8 9 6 6

D i a g n o s e d 1 9 9 5 –

2 0 0 1 . E n d F U :

2 0 0 4

2 o r m o r e c o m o r b i d i t i e s ,

d i a b e t e s m e l l i t u s a n d

p r e v i o u s c a n c e r

P r e v i o u s c a n c e r , C

V D

, D M

,

c e r e b r o v a s c u l a r d i s e a s e ,

d e m e n t i a , 2 o r m o r e

c o m o r b i d i t i e s , s t a g e ,

t r e a t m e n t ( R T , S T ,

a g e )

O v e r a l l a s w e l l a s r e l a t i v e

s u r v i v a l w a s m e a s u r e d f o r

e x c e s s m o r t a l i t y d u e t o B C

P r i m a r y t r e a t m e n t o f B C

p a t i e n t s w i t h s e r i o u s

c o m o r b i d i t y w a s l e s s

e x t e n s i v e t h a n t r e a t m e n t o f

t h o s e

w i t h o u t c o m o r b i d i t y

6 1

T a m m e m a g i 2 0 0 5 [ 1 4 ] 9 0 6

1 0

N u m b e r o f s e v e r e

c o m o r b i d i t i e s , r a c e , t y p e

o f c o m o r b i d i t y

A l l p a t i e n t s : 3 o r m o r e

c o m o r b i d i t i e s a d j u s t e d

f o r s t a g e , a g e , E R ,

s u r g e r y , c h e m o t h e r a p y ,

r a d i o t h e r a p y


A A h a d m o r e d i a b e t e s a n d

h y p e r t e n s i o n . A f t e r

a d j u s t m e n t f o r t h e s e 2

c o m o r b i d i t i e s d i s p a r i t y

d i s a p p e a r e d

6 2

M e u n i e r - C a r p e n t i e r

2 0 0 5 [ 5 5 ]

9 0 9 / 9 1 8 a g e : 2 5 – 8 1

1 1 . 3

T i e 2

–

U V : V E G F R - 2 ,

V E G F R - 2


V E G F R - 1 a n d T i e 2 w e r e

r e p o r t e d a s i n d e p e n d e n t

p r o g n o s t i c f a c t o r s c o r r e c t e d

f o r T , G , H

t y p , i n a l l

p a t i e n t s a n d N -


123



T a





f o l l o w - u p






R e m a r k s

6 3

T a i 2 0 0 5 [ 4 0 ]

6 1 8 4 I n a m m a t o r y B C

N R

. D i a g n o s e d

1 9 7 3 – 1 9 9 5 .

E n d F U : 2 0 0 0

P e r i o d o f d i a g n o s i s


w a s m e a s u r e d . P r o g n o s i s h a s

i m p r o v e d o v e r t h e d e c a d e s

d u e t o m o r e a g g r e s s i v e

t h e r a p y

6 4

L o u w m a n 2 0 0 5 [ 7 1 ]

4 9 2 T 1 – 2 N 0

> 1 0 y r s

M A I

O S : a g e , T

B C S : M A I

O S : H T y p , t h e r a p y ,

p e r i o d o f

d i a g n o s i s . B C S :

t h e r a p y , p e r i o d o f

d i a g n o s i s , a g e , T ,

H t y p

O v e r a l l ( O S ) a s w e l l a s r e l a t i v e

s u r v i v a l ( B C S ) w a s m e a s u r e d


H i g h e r M A I w a s a s i g n i c a n t

p r o g n o s t i c f a c t o r f o r N – a n d N + ,

b u t o n l y d u r i n g t h e r s t 1 0 y r s

o f F U

6 5

A r r i g a d a 2 0 0 6 [ 8 ]

2 4 1 0 T £ 7 c m N 1 – 2

1 9

T , s k i n x a t i o n , m u s c l e

x a t i o n , G

, N , a g e

T o t a l F U : T , N , G

, a g e < 3 5 ,

a g e ‡ 5 5

F U 0 – 5 y r s : T , N

, G , a g e

‡ 5 5

F U 5 – 1 0 y r s : N , G , a g e

< 3 5 , a g e ‡

5 5

F U 1 0 – 1 5 y r s : N

> 1 0 , a g e

> 5 5 . F U 1 5 – 2 0 y r s : a g e ‡ 6 5


L o n g - t e r m e f f e c t o f

p r o g n o s t i c f a c t o r s v a n i s h i n g

6 6

N e w m a n 2 0 0 6 [ 2 9 ]

9 0 , 1 2 4 . W h i t e

A m e r i c a n : 7 6 , 1 1 1 .

A A : 1 4 , 0 1 3

A g e , s t a g e , S E S

M e t a - a n a l y s i s . A f r i c a n

A m e r i c a n i s a n i n d e p e n d e n t

p r e d i c t o r o f p o o r o u t c o m e f o r

o v e r a l l s u r v i v a l a n d b r e a s t

c a n c e r s p e c i c m o r t a l i t y

6 7

M e n v i e l l e 2 0 0 6 [ 2 4 ]

4 0 7 , 4 3 5

w o m e n

f o l l o w e d f o r B C

d e a t h ( N : 1 4 0 8 )

W o m e n w h o

d i e d o f B C i n

1 9 6 8 – 9 6

L e v e l o f e d u c a t i o n b y

p e r i o d o f d i a g n o s i s

B r e a s t c a n c e r d e a t h a m o n g

w o m e n w i t h t h e h i g h e s t

e d u c a t i o n c o m p a r e d t o

w o m e n w i t h t h e l o w e s t

e d u c a t i o n i n 1 9 6 8 – 7 4 w a s

0 . 4 3 ; a n d i n 1 9 9 0 – 9 6 : 1 . 1 7

( N S )

6 8

B o u c h a r d y 2 0 0 6 [ 2 5 ]

3 9 2 0 a g e < 7 0

N R

. D i a g n o s e d

i n 1 9 8 0 – 2 0 0 0

S E S

S E S c o r r e c t e d f o r a g e ,

p e r i o d o f d i a g n o s i s ,

m a r i t a l s t a t u s , c o u n t r y

o f

b i r t h , H t y p , E R

,

d e t e c t i o n m e t h o d , s t a g e ,

s e c t o r o f c a r e , t h e r a p y


L o w e s t S E S h a d l e s s

f r e q u e n t l y s c r e e n - d e t e c t e d

c a n c e r s , l e s s s t a g e I , l e s s

l o b u l a r B C

, l e s s B C T , l e s s

l y m p h n o d e d i s s e c t i o n


123



T a





f o l l o w - u p






R e m a r k s

6 9

S i e g e l m a n n - D a n i e l i

2 0 0 6 [ 1 1 7 ]

9 9 2 , a g e

‡ 7 0

6 . 9

B e i n g i n w h e e l c h a i r , r e n a l

i n s u f c i e n c y , d e m e n t i a ,

C H F , c a r d i a c a r r h y t h m i a ,

D M

, I H D

, o s t e o p o r o s i s ,

P V D

, c e r e b r o v a s c u l a r

d i s e a s e , C O P D

,

P a r k i n s o n ’ s d i s e a s e ,

v a l v u l a r h e a r t d i s e a s e

I n s t a g e 1 A - 2 A : a g e , C H F ,

D M

, P V D

, s t a g e , c a r d i a c

a r r h y t h m i a , P a r k i n s o n ’ s

d i s e a s e , r e n a l

i n s u f c i e n c y

I n s t a g e 2 B - 4 : G , s t a g e ,

N ,

w h e e l c h a i r - b o u n d , r e n a l

i n s u f c i e n c y , C O P D

, a g e ,

D M

S y s t e m i c t h e r a p y


C H F : C a r d i a c H e a r t F a i l u r e .

D M : D i a b e t e s M e l l i t u s . I H D :

I s c h e m i c H e a r t D i s e a s e . P V D :

P e r i p h e r a l H e a r t D i s e a s e .

C O P D : C h r o n i c O b s t r u c t i v e

P u l m o n a r y D i s e a s e . R o l e o f

c o m o r b i d i t y v a r i e s b y a g e

7 0

P r i t c h a r d 2 0 0 6 [ 6 8 ]

6 3 9 p r e m e n o p a u s a l N + 1 0

H e r 2 a m p l i c a t i o n

H e r 2 c o r r e c t e d f o r a g e , N

,

E R , t y p e

o f s u r g e r y


T h o s e w i t h a m p l i e d H e r 2

h a v e i m p r o v e d s u r v i v a l w i t h

C E F

7 1

L e e 2 0 0 6 [ 5 2 ]

( A ) A d j u v a n t t h e r a p y – :

9 9 0 . ( B ) A d j u v a n t

t r e a t m e n t + : 1 7 6 5

G r o u p A : 1 3

G r o u p B : 6 . 8 .

L V

I

G r o u p A : T , G , L V I , H t y p

G r o u p B : T , G , L V I ,

c h e m o t h e r a p y , h o r m o n a l

t h e r a p y

B : E R , a g e ,

H t y p



F o r p a t i e n t s w i t h o u t a d j u v a n t

t r e a t m e n t , r o l e o f G i n s u r v i v a l

w a s h i g h e r i n t h e r s t 5 y r s .

R o l e o f H t y p w a s n o t s i g n i c a n t

f o r t h e r s t 5 y r s o f F U

a

i n d i c a t e s t h e o v e r l a p p i n g p a t i e n t s

u s e d b y t h e s a m e a u t h o r t o a n s w e r a n o t h e r r e s e a r c h q u e s t i o n ; y r s : y e a r s ; U V : U n i v a r i a t e a n a l y s i s . M V : M u l t i v a r i a t e a n a l y s i s . M S : M e n o p a u s a l S t a t u s ; T :

T u m o u r s i z e ; N : N o d a l i n v o l v e m e n t ; H t y p : H i s t o l o g i c a l t y p e ; M I : M i t o t i c I n d e x ; G : G r a d e ; P R : P r o g e s t e r o n e R e c e p t o r s t a t u s ; E R : O e s t r o g e n R e c e p t o r s t a t u s ; P C N A : p r o l i f e r a t i n g c e l l n u c l e a r

a n t i g e n ; m o s : m o n t h s ; N R : N o t R e p o r t e d ; A A : A f r i c a n A m e r i c a n ; a g e : i s i n y e a r a n d i n d i c a t e a g e a t p r i m a r y b r e a s t c a n c e r u n l e s s o t h e r w i s e s t a t e ; N P I : N o t t i n g h a m

P r o g n o s t i c I n d e x ; L V I :

L y m p h o v a s c u l a r I n v a s i o n ; ( P r o g n o s t i c f a c t o r ) * ( P r o g n o s t i c f a c t o r ) : i n t e r a c t i o n b e t w e e n t w o f a c t o r s ; B M I : B o d y M a s s I n d e x ; A M C : A v e r a g e M i c r o v e s s e l C o u n t ; M A I : M i t o t i c A c t i v i t y I n d e x ;

A I : A p o p t o s i s I n d e x ; F U : F o l l o w - u p ; S E S : S o c i o e c o n o m i c S t a t u s ; B V I : B l o o d v e s s e l I n v a s i o n ; L M V D : L y m p h a t i c M i c r o v e s s e l D e n s i t y ; L R : l o c a l r e c u r r e n c e ; C V D : C a r d i o v a s c u l a r D i s e a s e ;

D M : D i a b e t e s M e l l i t u s ; R T : r a d i o t h e r a p y ; S T : S y s t e m i c t h e r a p y ; V E G F R : V a s c u l a r E n d o t h e l i a l G r o w t h F a c t o r R e c e p t o r ; O S : O v e r a l l s u r v i v a l ; B C S : B r e a s t C a n c e r S p e c i c S u r v i v a l ; N S : n o t

s i g n i c a n t ; C H F : C a r d i a c H e a r t F a i l u r e ; I H D : I s c h e m i c H e a r t D i s e a s e . P V D : P e r i p h e r a l H e a r t D i s e a s e . C O P D : C h r o n i c O b s t r u c t i v e P u l m o n a r y . C E F : c y c l o p h o s p h a m i d e , e p i r u b i c i n a n d

u o r o u r a c i l


123



T a

b l e 2

S e l e c t e d p r o g n o s t i c f a c t o r s f o r l o n g - t e r m o v e r a l l m o r t a l i t y o f b r e a s t c a n c e r ( B C ) p a t i e n t s

P a t i e n t g r o u p s b a s e d

H a z a r d r a t i o ( H R ) f o r

o v e r a l l f o l l o w - u p o r

s u r v i v a l p r o b a b i l i t y ( S )

1 0 y e a r s a f t e r d i a g n o s i s

M o r p h o l o g y b a s e d



s u r v i v a l p r o b a b i l i t y

( S ) 1 0 y e a r s a f t e r

d i a g n o s i s

M o l e c u l a r b a s e d



s u r v i v a l p r o b a b i l i t y

( S ) 1 0 y e a r s a f t e r

d i a g n o s i s

A g e a t d i a g n o s i s [ 8 ]

H R :

L y m p h n o d e s t a t u s [ 3 1 ]

H R :

H E R 2 [ 6 9 ]

H R :

< 3 5 v s . 3 5 – 4 4

1 . 4 ( P : 0 . 0 7 )

N ‡ 1 v s . N 0

2 . 4 ( 1 . 9 – 2 . 9 )

> 5 0 0 v s . £ 5 0 0

1 . 8 2 ( 1 . 1 – 2 . 9 )

4 5 – 5 4 v s . 3 5 – 4 4

1 . 1 ( n s )

M e t a s t a s e s v s . N 0

2 2 . 7 3 ( 1 6 . 1 – 3 2 . 2 )

O n l y i n n o d e - p o s i t i v e

5 5 – 6 4 v s . 3 5 – 4 4

2 . 0 ( P : 0 . 0 0 0 )

6 5 – 7 5 v s . 3 5 – 4 4

2 . 5 ( P : 0 . 0 0 0 )

P e r i o d o f d i a g n o s i s [ 1 6 ]

R e l a t i v e s u r v i v a l b :

T u m o u r s i z e ( m m ) [ 3 1 ]

H R :

C e l l p r o l i f e r a t i o n i n d e x

H R :

1 9 7 2 – 1 9 7 6

5 9 %

T 1 0 – 1 4 v s . T 1 – 9

1 . 2 ( 0 . 8 – 1 . 9 )

( M A I )

1 9 7 7 – 1 9 8 6

6 4 %

T 1 5 – 1 9 v s . T 1 – 9

1 . 7 ( 1 . 1 – 2 . 6 )

> 1 0 v s . £ 1 0 [ 1 0 ]

1 . 0 2 ( 1 . 0 0 – 1 . 0 3 )

1 9 8 7 – 1 9 9 1

7 0 %

T 2 0 – 2 9 v s . T 1 – 9

2 . 5 ( 1 . 6 – 3 . 9 )

O n l y i n n o d e - p o s i t i v e

p a t i e n t s

T 3 0 – 4 9 v s . T 1 – 9

3 . 8 ( 2 . 4 – 6 . 0 )

T ‡ 5 0 v s . T 1 – 9

4 . 6 ( 2 . 9 – 7 . 6 )

T i m e a f t e r d i a g n o s i s [ 1 6 ]

R e l a t i v e s u r v i v a l :

T u m o u r g r a d e [ 4 4 ]

H R :

G e n e e x p r e s s i o n p r o l e [ 7 4 ]

S :

0 v s . 5 y r s a f t e r d i a g n o s i s

I I v s . I

2 . 5 ( 1 . 0 – 6 . 1 )

5 5 % v s . 9 5 %

R e g i o n a l B C

7 9 % v s . 8 4 %

I I I v s . I

5 . 7 ( 2 . 6 – 1 2 . 4 )

P o o r v s . g o o d s i g n a t u r e f

L o c a l l y a d v a n c e d B C

5 3 % v s . 6 8 %

S o c i o e c o n o m i c s t a t u s [ 2 6 ]

H R :

T u m o u r t y p e [ 3 4 ]

S :

E R / P R s t a t u s [ 3 0 ]

H R :

I n t e r m e d i a t e v s . a f u e n t

1 . 2 ( 1 . 0 – 1 . 4 )

P o o r v s . e x c e l l e n t d , e

< 5 0 % v s . > 8 0 %

P o s i t i v e v s . n e g a t i v e

0 . 3 8 ( 0 . 0 2 – 1 . 0 6 )

D e p r i v e d v s . a f u e n t

1 . 2 ( 0 . 9 9 – 1 . 5 3 )

L i f e s t y l e

H R :

B o d y M a s s I n d e x

< 2 1 v s . 2 9 + k g / m

2

1 . 4 ( 0 . 9 7 – 2 . 0 0 ) [ 8 5 ] c

P h y s i c a l a c t i v i t y

< 3 v s . 2 3 . 9 M E T - h / w k a

0 . 5 6 ( 0 . 4 – 0 . 8 ) [ 8 7 ]

H R : H a z a r d r a t i o c a l c u l a t e d w i t h i n m u l t i v a r i a t e a n a l y s i s o f b r e a s t c a n c e r p a t i e n t s f o l l o w e d f o r a m e d i a n / m e a n o f 1 0 y e a r s o r l o n g e r a

M e t a b o l i c e q u i v a l e n t t a s k h o u r s p e r w e e k ; b

E s t i m a t e s

t a k e n f r o m g r a p h ; c

H i g h e r a l c o h o l i n t a k e n o s i g n i c a n t e f f e c t o n m o r t a l i t y . S i g n i c a n t t r e n d o f h i g h e r m o r t a l i t y f o r l o w e s t c o m p a r e d t o h i g h e s t q u i n t i l e s o f b r e , l u t e i n

a n d z e a x a n t h i n , c a l c i u m

& p r o t e i n i n t a k e ; d

B e c o m e s l a r g e r a s n u m b e r s o f i n v o l v e d l y m p h n o d e s i n c r e a s e s [ 8 ] ; e

E x c e l l e n t p r o g n o s i s : t u b u l a r , i n v a s i v e c r i b r i f o r m , m

u c i n o u s , t u b u l o l o b u l a r . P o o r p r o g n o s i s : m i x e d

l o b u l a r , s o l i d l o b u l a r , d u c t a l a n d m i x e d d u c t a l l o b u l a r ; f

u n a d j u s t e d e s t i m a t e s


123



other prognostic factors in determining survival for long-term survivors still needs to be determined.

The role of early detection

Increased awareness among women and improvement indiagnostic procedures have enabled earlier and better

detection of BC. Trials on population screening have re-ported 21–29% reduction in BC mortality for women in-vited for screening within 14–16 years of follow-up [ 19,97]. Screening identied tumours at an early stage conse-quently, survival improved [ 98, 99]. Screening also iden-tied patients with slowly growing tumours who mightreceive unnecessarily aggressive cancer treatment. Thus,Joensuu et al. [ 100 ] examined recurrence rates among pa-tients detected by screening compared to those detectedoutside screening. After adjusting for tumour aggressive-ness (tumour size, nodal status, grade, age, treatment, PRstatus, HER-2), hence eliminating bias towards detection of

indolent cancers (length bias), the benet of screening forthe prognosis for BC patients remained evident.[ 100 ] Thissuggests that other factors explain the indolent behaviourof BC detected by screening. Hence, until this factor isestablished, detection mode should probably be consideredas a prognostic factor and thus be taken into account inpatient management.

The role of treatment

Improvement in BC treatment has undoubtedly also in-creased the long-term survival of BC patients [ 101 ], as

reected by the improved overall survival across all BCstages [ 16]. Using historical data from population-basedstudies in periods when effective treatment was not avail-able, it was estimated that without treatment only 4% of BC patients would survive 10 years or longer [ 102 ]. BCtreatment guidelines have been modied continuously inthe last 28 years, tailored to most of the prognosticatorsmentioned earlier [ 51]. Effectiveness of various treatmentmodalities has been summarized by others who concludethat radiation, chemotherapy and hormonal therapy mayreduce long-term mortality by up to 57% [ 66, 103 –105 ].Emerging new therapeutic approaches using a monoclonal

antibody directed against HER-2 have yielded improvedshort-term survival for advanced stage [ 106 ] as well asoperable BC patients [ 107 ]. Quality of treatment asindicated by loco-regional failure [ 108 ], surgeon workload[109 ] or hospital volume [ 110 ], may affect survivalalthough its role on long-term survival still needs conr-mation. In conclusion, on the one hand we have observed ashift in stage towards less aggressive cancers; on the otherhand, better and more (systemic) treatment has becomeavailable, leading to improved survival for BC patients.

Conclusion

The prognosis of BC has become relatively good, with cur-rent 10-year relative survival about 70% in most westernpopulations [ 16, 111 ], especially if up-to-date statisticalmethod such as the period analyses is used [ 111 ] (Table 1).Even better, the longer patients survive their BC the higher

their survival chance [ 16]. Our review shows conventionalprognostic factors of survival, such as tumour size, lymphnode status and grade, remain the most important determi-nants of 10-year survival for BC patients (Table 2). Moststudies agreed on the value of MAI and LVI for prediction of long-term survival. The inuence of host factors includingage, race/ethnicity or socio-economic factors and tumour-related factors such as histological type and angiogenesisdiminishes after correction for other factors. For most recentmarkers such as Her2, gene proling, p53 mutation and uPAlevel longer follow-up is needed. Recurrence, metastasesanda second cancer double the burden of disease thus increaserisk of mortality. Similarly, co-occurrence with other dis-eases is in no doubt decrease survival.

Healthier lifestyle generally increases long-term sur-vival. Modiable risk factors (such as alcohol consumptionand obesity) not only affect incidence but also tumour’clinical behaviour and thus survival.

Although a lot is known about the prognosis for BCpatients, effect of traditional prognostic factors appears toattenuate over time, leaving room for studies on the role of other and newer factors for long-term survival.

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an overview of prognostic factors for long-term survivors of breast cancer

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