896
Chapter 33
was not observed between nonpalpable and palpable tumors
in women younger than 50 years (mean tumor size, 4.0 and
3.4 cm, respectively). These results led the authors to con
clude that physical examination and mammography were
less sensitive in women 20 to 49 years old when compared
with women 50 years or older. They suggested that “tumors
in young women are nonpalpable, not because they are small,
but because of background density of the mammary tissue
or because of the more diffuse growth pattern of tumors at
this age. These are exactly the same reasons mammography
is less sensitive in young women.” The addition of FNA or
needle core biopsy for abnormalities detected by mammog
raphy and clinical examination constitutes the “triple test”
for the diagnosis of breast tumors, a method that improves
diagnostic accuracy, especially in younger women.
64
Pathology
Most pathologic features of breast carcinoma do not differ
appreciably in adults who are relatively young or old.
65–68
Tu
mor size is not significantly different when young and elderly
patients are compared.
67
Approximately 50% of patients have
tumors 2 cm or smaller, 40% have tumors in the 2.1- to 5.0-cm
range, and the rest have tumors larger than 5 cm. The left breast
is more often affected than the right in both age extremes. The
location of the tumor (lateral vs. medial-central), the overall
frequency of bilaterality, and concurrent bilaterality are not
significantly different at the extremes of the age distribution.
Several differences with respect to tumor type exist at the
extremes of age.
66
Patients younger than 35 have a higher
proportion of medullary carcinoma, and lower proportions
of infiltrating lobular (2.0% vs. 11.0%) and of mucinous car
cinoma (1.0% vs. 7.0%), in comparison with patients older
than 75. A marked lymphocytic reaction occurs in a higher
proportion of women younger than 35 than in the elderly
group (34% vs. 12%).
Collins et al.
69
analyzed clinical and pathologic data for
657 patients with intraductal carcinoma (ductal carcinoma
in situ
[DCIS]) to identify features that might explain the
greater risk for local recurrence in young women after breast-
conserving therapy. Four age groups were compared, with
the youngest consisting of 111 women less than 45 years of
age at diagnosis, who proved to have significantly more ex
tensive DCIS and more frequent lobular cancerization than
women older than 45. DCIS was detected by mammography
significantly less often in women younger than 45 years than
in any of the older cohorts. There was no statistically signifi
cant relationship between age and the following features of
DCIS: architectural type, nuclear grade, comedonecrosis, or
the expression of receptors for ER, PR, or epidermal growth
factor receptor 2 (EGFR2).
Prognostic and Predictive Markers
in Invasive Carcinoma
Studies of growth rate and tumor cell kinetics suggest an inverse
relationship between patient age at diagnosis and the prolifera
tive activity in the invasive carcinoma.
70,71
Growth rate tends to
with mastectomy. The disease-free interval was shorter in
patients with hormone receptor–positive carcinoma after a
median follow-up of 78 months. The overall 5-year survival
was 80%, suggesting that the prognosis of patients in this age
group is improved by earlier diagnosis and the use of mod
ern treatment modalities in addition to surgery.
Patients 40 to 49 Years of Age
Most studies of clinical issues in the diagnosis of breast
carcinoma in younger women have focused on the relatively
large group of patients 40 to 49 years of age. A report of
809 consecutive patients biopsied for nonpalpable, mam
mographically detected lesions revealed carcinoma in 5% of
biopsies prior to age 40, in 15% of biopsies in the 40- to
49-year age group, and in 34% of biopsies from women
older than 50 years.
61
Twenty-five percent of carcinomas
in women 40 to 49 years old and 16% in women 50 years
or older were noninvasive. Mean tumor size was the same
in both groups (1.5 cm), but nodal metastases were present
more often in the 40- to 49-year age group (25%) than in the
group 50 years or older (17%).
McPherson et al.
62
investigated the relationship of method
of tumor detection to prognosis in women 40 to 49 years of
age using a database of patients diagnosed in North Dakota,
South Dakota, and Minnesota. When compared with the
risk of dying from carcinomas detected by mammography,
the RRs of dying from carcinomas detected by breast self-
examination (BSE) (2.5), clinical breast exam (CE) (2.7),
or discovered by the patient incidentally (2.8) were signifi
cantly greater. The mean size of mammographically detected
tumors (1.9 cm) was significantly smaller than those in the
CE (2.3 cm), BSE (2.8 cm), and incidental (2.9 cm) groups.
After adjusting for stage (tumor size and nodal status), the
RRs of dying of carcinomas were greater when detected by
BSE (1.5), CE (1.9), or incidentally (1.6), when compared
with tumors detected by mammography. These results sug
gest that mammography makes a contribution to improv
ing the prognosis of women with carcinoma 40 to 49 years
of age. The implications of these observations for mammo
graphic screening in this age group and in women younger
than 40 years remain controversial.
Clinical problems encountered in the diagnosis of breast
carcinoma in women 49 years and younger were detailed
in a report by Lannin et al.
63
The authors analyzed the re
sults of mammography and physical examination in a con
secutive series of patients evaluated in a university hospital
clinic in order to compare women 20 to 49 years of age
with those 50 years or older. The positive predictive value
(PPV) of mammography was 28% for women younger than
50 and 53% in those 50 years or older. The PPV of an abnor
mal physical examination resulting in biopsy was 11% and
57% in women younger than 50 years and 50 or older, re
spectively. There was also a statistically significant differ
ence in the sensitivity of mammography between patients
younger than and 50 years or older (68% and 91%, respec
tively). The sensitivity of physical examination did not dif
fer significantly between the two groups. This discrepancy
