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ORIGINAL ARTICLE

Invasive Apocrine Carcinoma of the Breast:

Clinicopathologic Features of 57 PatientsKimihiro Tanaka, MD,* Shigeru Imoto, MD,* Noriaki Wada, MD,* NorikoSakemura, MD,* and Kahiro Hasebe, MD

*Breast Surgery Division; andSurgical Pathology Section, Clinical Laboratory Division, NationalCancer Center Hospital East, Kashiwa, Chiba, Japan

n Abstract: Apocrine carcinoma is a rare, unique, and morphologically distinctive type of invasive ductal carcinoma(IDC). The features of invasive apocrine carcinoma (IAC) and their possible prognostic implications have not been fullyinvestigated. To this end, we examined the clinicopathologic characteristics and outcome of patients with IAC and com-pared these factors with those of patients with IDC. Out of 2,055 breast cancer patients who had undergone breast surgerybetween 1995 and 2005, 57 patients of IAC and 1,583 patients of IDC were analyzed. The mean ages of the patients withIAC and of those with IDC were 58.5 10.9 years and 54.4 11 years, respectively (p = 0.006). The percentages ofpatients with axillary nodal metastasis and lymphatic invasion were significantly lower in the IAC group than in the IDCgroup (p = 0.03 and 0.02, respectively). The percentage of estrogen and progesterone receptor negativity was higher in theIAC group than in the IDC group (p < 0.001). After a median follow-up period of 49 months (range, 1133 months), seven(12%) patients with IAC and 244 (15%) patients with IDC had experienced recurrences. Three (5%) patients with IAC and125 (8%) patients with IDC died of recurrent breast cancer. No significant differences in the relapse-free survival (p = 0.83)and overall survival (p = 0.75) rates were observed between the two groups. Although IAC and IDC have different clinico-pathologic characteristics, the prognoses of patients with these diseases are similar. n

Key Words: apocrine carcinoma, axillary nodal metastasis, breast cancer, hormone receptor

Apocrine carcinoma is a rare tumor accounting for0.4 to 4% of all breast cancers (16). Despite anincreasing recognition of this tumor in recent years,the morphologic diagnostic criteria remain unclear.

Rosen stipulated that the term should be reserved for

neoplasms in which all or nearly all the epithelium

has apocrine cytologic features (7).

Since Krompecher first described apocrine carci-

noma in 1916 (8), its clinicopathologic characteris-

tics and prognosis have been described in several

reports (16,917). Apocrine carcinoma cells tend to

exhibit a loss of hormone receptors. With regard to

prognosis, invasive apocrine carcinoma (IAC) had

the same prognosis as invasive ductal carcinoma(IDC) in some reports, but these studies were

based on small numbers of patients with IAC. In

this report, we investigated the clinicopathologic

characteristics and outcomes of patients with IAC

whose clinical records had been included in our

database to clarify the biological differentiationbetween IAC and IDC.

MATERIALS AND METHODS

From January 1995 to August 2005, a total of

2,055 primary breast cancer patients underwent breast

surgery in the Breast Surgery Division of the National

Cancer Center Hospital East. The records of all these

patients were reviewed, and 61 patients (3%) were

diagnosed as having had apocrine carcinoma. Among

the patients with apocrine carcinomas, four did nothave an invasive component (intraductal apocrine car-

cinoma). Thus 57 patients with IAC were retrospec-

tively compared with 1,583 patients with IDC who

had been treated during the same time. The clinico-

pathologic features and the outcomes of these patients

were retrospectively examined.

In our institution, apocrine carcinoma was defined

as a neoplasm composed of 80% or more tumor cells

with abundant, granular eosinophilic cytoplasm, and

Address correspondence and reprint requests to: Kimihiro Tanaka,

Breast Surgery Division, National Cancer Center Hospital East, 6-5-1 Kas-

hiwanoha, Kashiwa, Chiba 277-8577, Japan, or e-mail: kimtanak@

east.ncc.go.jp.

2008, Copyright the AuthorsJournal compilation 2008 Blackwell Publishing, Inc., 1075-122X/08The Breast Journal, Volume 14 Number 2, 2008 164168


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round centrally to the eccentrically located malignant

nuclei containing prominent nucleoli. On the other

hand, neoplasms in which less than 80% of the tumor

cells exhibited apocrine cytologic features were defined

as IDC with apocrine features. Histologic grading was

performed according to the modified BloomRichard-son histologic grading scale for infiltrating carcinomas.

The estrogen receptor (ER) and progesterone receptor

(PgR) status was assessed using an enzyme immuno-

assay or immunohistochemistry. For the enzyme

immunoassays, the upper cutoff values for ER and

PgR in the cytosol fraction were set at 13 fmol mg

and 10 fmol mg of protein, respectively. Immuno-

staining for ER and PgR was considered positive when

a distinct nuclear localization was found in 10% or

more of the cells. The human epidermal growth

factor receptor type 2 (HER2) status was evaluated

using the Herceptest (DakoCytomation, Carpinteria,CA). Tumors were considered positive if 10% or more

tumor cells had distinct circumferential membrane

staining.

Statistical Analysis

Relapse-free survival was defined as the time until

the first occurrence of disease recurrence at any site.

Overall survival was defined as the time until death

from any cause. Statistical differences between the

two groups were analyzed using the chi-squared test

(or the Fishers exact probability test). Survivalcurves were produced according to the KaplanMeier

method and were compared using the log-rank test.

statmate III (for Macintosh) was used for the statis-

tical analysis. A p-value of


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with IAC and 125 (8%) patients with IDC died of

breast cancer. No significant differences in the relapse-

free survival (p = 0.83) and overall survival (p = 0.75)

periods of the two groups were observed. We alsoexamined the overall survival of patients stratified

according to nodal status and ER status. No signifi-

cant differences in overall survival were observed

between the two groups among patients without axil-

lary nodal metastases (p = 0.29), with axillary nodal

metastases (p = 0.49), with ER negativity (p = 0.27),

or with ER positivity (p = 0.74).

DISCUSSION

We reviewed several previously reported patients of

apocrine carcinoma (Table 3). Apocrine carcinoma

accounted for 3% of all breast cancers treated at our

institution. The incidence tended to be higher than

those mentioned in other reports. However, the inci-

dence of apocrine carcinoma varied considerably from

one report to another. Differences in the pathologic

criteria of apocrine carcinoma may result in the vari-

ety in the reported incidences.

Apocrine carcinoma has a unique hormone receptorprofile. The percentages of IAC patients with ER and

PgR positivity were significantly low (16% and 21%,

respectively). The reason for the low percentage of ER

Relapse-freesurvival(%)

Time after operation (years) Time after operation (years)

86420

IDC (n=1583)

IAC (n=57)

Overallsurvival(%)

0

86420 1010

100

80

60

40

20

0

100

80

60

40

20

)75=n(CAI

)3851=n(CDI

Figure 1. Relapse-free survival (p = 0.83)

and overall survival curves (p = 0.75) of

patients with invasive apocrine carcinoma

(full line) and invasive ductal carcinoma (dot-

ted line).

Table 2. Comparison of Recurrence and Survivalbetween Invasive Apocrine Carcinoma and Inva-sive Ductal Carcinoma

Invasive

apocrine

caricnoma

(n = 57)

Invasive

ductal

carcinoma

(n = 1583) p

Recurrence 7 244 0.83

Loco-regional 5 76

Distant 2 133

Distant with loco-regional 0 35

Survival

Death because of breast cancer 3 125 0.75

Table 3. The Comparison of Present Study with Other Studies

Author [year] (ref.)

No. of

patients

Incidence

reported

Age

mean

Tumor

size (cm)

Nodal

metastases

positivity ER positivity PgR positivity

Honma et al. [2005] (15) 52 37% (14 38) 4% (2 52) 6% (3 52)

Japeze et al. [2005] (11) 37 52.9 2.5 42% (14 33) 61% (22 36) 58% (21 36)

Takeuchi et al. [2004] (6) 33 1.6% 57.1 3.1 30% (10 33) 33% (8 24) 27% (6 22)

Sapp et al. [2003] (10) 15 13% (2 15) 7% (1 15)Matsuo et al. [2002] (13) 24 61 2.6 14% (3 22) 17% (4 24) 17% (4 24)

Leal et al. [2001] (17) 35 59 2.3 0% (0 9) 6% (2 35) 3% (1 34)

Tavassoli et al. [1994] (16) 37 0% (0 23)

Abati et al. [1990] (12) 72 54.2 1.8 11% (5 45) 40% (4 10) 50% (2 4)

Aoyagi et al. [1990] (5) 10 0.65% 58.1 3.5 50% (5 10)

dAmore et al. [1988] (9) 34 59 2.1 53% (18 34)

Gadaleanu et al. [1986] (4) 6 0.4% 48.6 2.6 0% (0 6)

Eusebi et al. [1986] (3) 4 4.0% 70.3 2.4 50% (2 4) 75% (3 4) 50% (2 4)

Mossler et al. [1980] (2) 6 0.4% 66.5 2.4 67% (4 6) 0% (0 6) 0% (0 6)

Frable et al. [1968] (1) 19 1.0% 41% (7 17)

Present study 57 3.0% 58.5 2.6 27% (15 56) 16% (9 57) 21% (12 57)

Total 441 1.2% 57.1 2.4 29% (97 336) 21% (56 263) 20% (52 254)

166 tanaka et al.


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and PgR positivity among patients with IAC is

unclear. Bratthauer et al. demonstrated that 9 out of

11 ER-negative lesions contained ER mRNA (18).

This result suggests that the mechanism for the pro-

duction of ER through the first transcriptional splice

region is intact and functional in most cases. There-fore, the immunohistochemical absence of ER in apo-

crine cells cannot be explained by an abnormal

message at these common sites and should be sought

at a downstream position in the pathway. Sap et al.

reported that the grade of IAC differentiation was cor-

related with the loss of ER and PgR and that apocrine

differentiation was linked to the overexpression of

androgen receptors (AR) (10). Gatalica also demon-

strated the increased expression of AR in patients with

apocrine-differentiated tumors, compared with that in

nonapocrine tumors (19). Although we did not investi-

gate the AR status in the present study, these resultssuggest that in addition to the loss of ER and PgR,

AR positivity may be a distinctive feature of apocrine

carcinoma.

In our study, the positive rates of axillary nodal

metastasis and lymphatic invasion among patients

with IAC were 27% and 18%, respectively. In

patients with IDC, axillary nodal metastasis, lympha-

tic invasion, and vascular invasion were more strongly

associated with tumor recurrence or death (2023).

IAC was characterized by a lower frequency of lymph

node metastasis and lymphatic invasion. These find-ings suggest that IAC may be less aggressive. Japeze

et al. reported that patients with IAC had a signifi-

cantly better outcome (11). On the other hand, the

patients with IAC tended to show a loss of hormone

receptors on their cancer cells. Breast cancer patients

with ER and PgR negativity generally have a poor

prognosis. In the present study, no significant differ-

ences in the relapse-free survival and the overall sur-

vival periods were seen between the IAC group and

the IDC group. These findings were consistent with

the results reported by other investigators (1,6,9,12).

Taken together, patients with IAC may have the sameprognosis as those with IDC.

In conclusion, IAC is thought to be a clinicopatho-

logically distinctive entity with different characteristics

from those of other breast lesions. Although we were

able to clarify some of the characteristics of apocrine

carcinoma, the prognosis of patients with IAC was

similar to that of patients with IDC. Further molecu-

lar biological study will be needed to understand the

clinicophathologic features of IAC.

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