Unusual Clinical Presentation of Carcinoma
897
proved not to be significantly related to recurrence risk, and
it was concluded that the higher local failure rate in patients
younger than 45 was related to smaller excision volumes in
this age group.
Arvold et al.
87
studied 1,434 consecutive patients with in
vasive breast cancer who received breast conservation ther
apy over a 10-year period ending 2006. Ninety-one percent
received adjuvant systemic therapy. The median follow-up
was 85 months, and the overall 5-year cumulative incidence
of local recurrence was 2.1%. The 5-year cumulative inci
dence of local recurrence was 5.0% for ages 23 to 46 years;
2.2% for ages 47 to 54 years; 0.9% for ages 55 to 63 years;
and 0.6% for ages 64 to 88 years. On multivariable analysis,
increasing age was associated with decreased risk of local
recurrence.
Carcinoma in Elderly Women
The Cancer and Leukemia Group B (CALGB) trial 9343 ex
amined the contribution of radiation after lumpectomy in
women aged 70 and older with ER-positive node-negative
breast carcinomas that were 2 cm or smaller.
88
After tumor
excision, the patients were randomized to tamoxifen alone
versus radiation plus tamoxifen. An update of this study
with a 10.5-year median follow-up showed that 98% of the
radiation plus tamoxifen group and 92% of the tamoxifen-
only group were recurrence free.
89
Based on the 6% lower
frequency of ipsilateral breast tumor recurrence for the ra
diation group, it was estimated that 300 women would have
to be radiated to prevent 20 local recurrences. The fact that
the two groups did not differ significantly in overall 10-year
survival and breast-cancer–specific survival suggests that
the small difference in the frequency of breast recurrence
did not significantly affect survival 10 years after initial
treatment.
Results of the ongoing Postoperative Radiation in
Minimal Risk Elderly Patients (PRIME II) trial
90
in the
United Kingdom may further define the effect of omis
sion of radiation in elderly patients with hormone recep
tor node-negative invasive carcinomas. Until then, the
advantages of radiation after breast conservation ther
apy in this subset of elderly patients should be weighed
against its morbidities, and the decision to radiate should
be individualized.
Genetic Considerations
Some special considerations are to be kept in mind regard
ing genetic abnormalities and breast carcinoma in young
adult women.
“Secretory carcinoma” is the most common malignant
epithelial neoplasm encountered in children. Its occurrence
in younger patients accounts for the previously used term
juvenile carcinoma, but it can be found in adult women of all
ages. Because secretory carcinoma almost always has a bal
anced chromosomal translocation, t(12:15)(p13;q25) that
leads to fusion of the
ETV6
and
NTRK3
genes,
91
it has been
referred to as “a genetically defined carcinoma entity.”
92
be reduced in breast carcinomas that arise in elderly women.
71
Others have reported that the presence of ALN metastases in
breast carcinoma patients 34 years or younger is significantly
related to p53 positivity and high proliferative index.
72
Walker et al.
73
found an inverse relationship between p53
immunopositivity and age, with positive staining in 67% and
37% of tumors from women 25 to 29 and 50 to 67 years of
age, respectively. Proliferative rate, assessed by Ki67 immu
nostaining, was also inversely related to age, with 72% of tu
mors in patients 25 to 29 classified as “high” compared with
40% in the group 50 to 67 years of age.
The proportion of ER-positive invasive carcinomas is
higher in postmenopausal than in premenopausal women,
and there is evidence indicating that the growth rate and
positive ER status of breast carcinomas are inversely re
lated.
71
Although breast carcinomas in younger women
are now more often detected before involving lymph nodes
than 10 years ago, a larger percentage is triple-negative.
74
The proportion of ER- and PR-positive tumors does not in
crease significantly with advancing age in postmenopausal
women 65 years or older.
75
Gennari et al.
76
reported that the
frequency of estrogen and progesterone positivity was sig
nificantly higher in postmenopausal women 65 years of age
or older when compared with postmenopausal women 50 to
64 years old. The older postmenopausal women had a sig
nificantly lower frequency of HER2-positive tumors. These
observations appear to support the perception that breast
carcinoma tends to have less aggressive biologic features and
a more favorable clinical course in the elderly. Nonetheless,
no significant differences in prognosis were observed when
patients younger than 35 and older than 75 were matched on
the basis of tumor stage.
66
Breast Conservation Therapy
Women 40 years of age or younger are more likely than
older patients to develop breast recurrences after breast-
conserving surgery and radiotherapy for invasive carci
noma.
77–81
This phenomenon has been attributed to more
frequent poorly differentiated carcinomas in this age group,
difficulty in determining extent of carcinoma intraopera
tively, and a high prevalence of carcinomas with an extensive
intraductal component or lymphatic emboli in peritumoral
tissue.
78
The addition of adjuvant chemotherapy appears to
lower the risk of breast recurrence in women younger than
35 years who are treated by breast conservation.
79,82,83
Chest
wall irradiation has been recommended if carcinoma is
present at or close to (less than 5 mm) the deep margin of a
mastectomy.
84
The risk of breast recurrence after breast con
servation does not appear to be affected by a family history
of breast cancer.
85
Vicini et al.
86
reported that patients younger than 45 years
of age had a significantly greater risk of breast recurrence
after conservation therapy (excision and radiotherapy) for
intraductal carcinoma than women who were 45 years or
older. The frequency of invasive recurrence was substan
tially greater in the younger age group. When the volume
of tissue was considered in the analysis, age at diagnosis
