RAMB Maio/Junho 2015

iacomazzi

284

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2015; 61(3):282-289

tively), women with breast cancer (frequency around 7%),

being most prevalent in the group diagnosed before 45

years, and among women with phyllodes tumors of the

breast (frequency of 5.7%).

27,28

Knowing these high rates in

Southern and Southeastern Brazilian regions, a strategy is

urgently needed to properly identify high risk patients from

LFS/LFL families, especially among pediatricians.

inversely proportional to age at diagnosis of the first tu-

mor: the relative risk of a second tumor and confidence

intervals (CI) were 83 (36.9-87.6), 9.7 (4.9-19.2), and 1.5

(0.5-4.2) for patients originally diagnosed at the ages of

0-19, 20-44, or ≥45 years respectively, and 5.3 (2.8-7.8) when

data for all ages were pooled. Decreasing age at diagnosis

has been observed in successive generations of carriers,

17-19

resembling the anticipation (Table 2). It has also been sug-

gested that carriers of germline

TP53

mutations are more

susceptible to radiation-induced tumors.

17,20-22

The incidence of LFS/LFL has been estimated at

1:2,000-5,000 in Europe and North America.

23,24

However,

in Brazil, case series of patients from the Southern and

Southeastern regions suggest that a particular

TP53

germ-

line mutation, p.R337H, occurs at a frequency of 1 in 300

in the general population.

25,26

It is exceedingly common

among children with adrenocortical and choroid plexus

tumors (approximate frequencies of 80 and 100%, respec-

TABLE 1

Clinical criteria for Li-Fraumeni and Li-Fraumeni-like syndromes.

Clinical criteria

Description

Classical LFS

(Li, Fraumeni et al., 1988)

I-

sarcoma diagnosed in childhood/young adulthood (≤ 45 years)

and

II-

first-degree relative with any cancer in young adulthood (≤ 45 years)

and

III-

first- or second-degree relative with any cancer diagnosed in young adulthood (≤ 45 years)

sarcoma

diagnosed at any age.

LFL – Birch

(Birch, Hartley et al., 1994)

I-

childhood cancer (at any age) or sarcoma, CNS tumor, or ACC in young adulthood (≤ 45 years)

and

II-

first- or second-degree relative with LFS-spectrum cancer (sarcoma, BC, CNS tumor, ACC, leukemia)

at any age

and

III-

first- or second-degree relative with any cancer diagnosed at age < 60 years.

LFL – Eeles 1 (Eeles, 1995)

Eeles 2 (Eeles, 1995)

I-

at least 2 first- or second-degree relatives with LFS-spectrum cancer (sarcoma, BC, CNS tumor, ACC,

leukemia, melanoma, prostate cancer, pancreatic cancer) diagnosed at any age

I-

sarcoma diagnosed at any age

and

II-

at least 2 other tumors diagnosed in one or more first- or second-degree relatives: BC at age < 50

years; CNS tumor, leukemia, ACC, melanoma, prostate cancer, pancreatic cancer at age < 60 years;

sarcoma at any age.

LFL – Chompret

(Frebourg, Abel et al., 2001)

I-

diagnosis of sarcoma, CNS tumor, BC, ACC at age < 36 years

and

II-

first- or second-degree relative with any of the above cancers (except BC if proband had BC)

relative

with multiple primary tumors at any age

III-

multiple primary tumors, including two of the following: sarcoma, CNS tumor, BC, or ACC, with the

first tumor diagnosed at age < 36 years regardless of family history;

IV-

ACC at any age, regardless of family history.

LFL – Modified Chompret

(Bougeard, Sesboüé et al., 2008; Tinat,

Bougeard et al., 2009)

I-

index case with LFS-spectrum cancer (sarcoma, BC, CNS tumor, ACC, leukemia, bronchioloalveolar

carcinoma) occurring at age < 46 years

and

II-

a first- or second-degree relative with LFS-spectrum cancer occurring at age < 56 years (except BC if

the index case has BC as well),

multiple tumors;

III-

index patient with multiple tumors, at least two of which are in the LFS spectrum, the first occurring

at age < 46 years;

IV-

ACC or choroid plexus carcinoma occurring at any age or BC occurring at age < 36 years without

BRCA1

BRCA2

mutations.

ACC: adrenocortical carcinoma; BC: breast cancer; CNS: central nervous system; LFS: Li-Fraumeni syndrome; LFL: Li-Fraumeni-like syndrome.

TABLE 2

Risks for second primary tumor in patients with

Li-Fraumeni and Li-Fraumeni-like syndromes according to

age at diagnosis of the first tumor.

Age at diagnosis of 1

primary

tumor (years)

Relative risk of a second

primary tumor (95%CI)

0-19

83.0 (36.9-87.6)

20-44

9.7 (4.9-19.2)

≥45

1.5 (0.5-4.2)

All ages

5.3 (2.8-7.8)

Source: Hisada et al.