This document reviews rare types of breast cancer. It summarizes information on 16 epithelial subtypes classified by the World Health Organization, including histopathology descriptions and clinical parameters. While rare cancers cannot be studied through large randomized trials, this review aims to provide clinicians an understanding to help determine optimal treatment approaches. It discusses cancers such as tubular carcinoma and mucinous carcinoma, which typically have a good prognosis and are often estrogen receptor positive with low lymph node involvement.

1. review Annals of Oncology 20: 1763–1770, 2009
doi:10.1093/annonc/mdp245
Published online 14 July 2009
Breast carcinoma—rare types: review of the literature
R. Yerushalmi1*, M. M. Hayes2 & K. A. Gelmon1
1
Division of Medical Oncology and 2Department of Pathology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
Received 23 February 2009; accepted 26 March 2009
Invasive breast cancer is a heterogeneous disease in its presentation, pathological classification and clinical course.
However, there are more than a dozen variants which are less common but still very well defined by the World Health
Organization (WHO) classification. The rarity of many of these neoplasms does not allow large or randomized studies
to define the optimal treatment. Many of the descriptions of these cancers are from case reports and small series. Our
review brings updated information on 16 epithelial subtypes as classified by the WHO system with a very concise
histopathology description and parameters helpful in the clinic. The aim of our review is to provide a tool for breast
cancer caregivers which will enable a better understanding of the disease and its optimal approach to therapy. This
may also stand as a clinical framework for a future understanding of these rarer breast cancers when gene analysis
review
work is reported.
Key words: breast carcinoma, epithelial breast cancer, prognosis, treatment, triple negative, World Health
Organization classification
introduction definition of breast cancer. The rarity of many of these
neoplasms does not allow large or randomized studies to define
Invasive breast cancer is a heterogeneous disease in its the optimal treatment. Many of the descriptions of these
presentation, pathological classification and clinical course. cancers are from case reports and small series.
Most tumors are derived from mammary ductal epithelium, Our review brings updated information on 16 epithelial
principally the terminal duct-lobular unit, and up to 75% of the subtypes as classified by the WHO system [1] with a very
diagnosed infiltrating ductal carcinoma are defined as invasive concise histopathology description and parameters helpful in
ductal carcinoma, not otherwise specified (IDC-NOS). The the clinic. The aim of our review is to provide a tool for breast
second most common epithelial type is invasive lobular cancer caregivers which will enable a better understanding of
carcinoma which comprises of 5%–15% of the group. the disease and its optimal approach to therapy. This may also
However, there are more than a dozen variants which are less stand as a clinical framework for a future understanding of
common but still very well defined by the World Health these rarer breast cancers when gene analysis work is reported.
Organization (WHO) classification. Our review is based on Pubmed research updated to
Recently, there has been an increased emphasis on the December 2008.
immunohistochemical and genetic profile of tumors and these
classifications are evolving as a standard part of the diagnostic
process. This novel approach pushes aside traditional good prognosis, ER positive
descriptive definitions. An estrogen receptor (ER)-negative
ductal (NOS) as well as adenoid cystic, acinic and metaplastic Findings are summarized in Table 1.
carcinoma may all receive the title of triple-negative disease and
this may affect decision making for those less familiar with the tubular carcinoma
nuances of the rare tumor types. Furthermore, the classification definition and epidemiology. The definition of a tubular
using gene expression profile was established using a cohort of carcinoma (TC) requires tumor purity with 90% tubular
ductal carcinoma NOS, without including cancers of special architecture. The characteristic finding histologically is open
types. We therefore indicate that it is extremely important to tubules composed of single layer of epithelial cells and cellular
highlight what is known about the different behavior of each desmoplastic stroma. Nuclear grade is low. TC comprises of
tumor and gather together the published data with the goal of 0.7%–10.3% of the invasive epithelial breast cancer (IEC) and is
marrying the rare tumor types with a current molecular more likely to occur in postmenopausal women. A population-
based study of nodal metastases with 171 TC patients has found
the proportion of cases with axillary nodal involvement at
*Correspondence to: Dr R. Yerushalmi, Division of Medical Oncology, British Columbia
Cancer Agency, 600 W 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E6. Tel: presentation to be lower in TC than in the grade 1 IDC group
+1-604-877-6000-2594; Fax: +1-604-877-0585; E-mail: ryerushalmi@bccancer.bc.ca (12.9% and 23.9%, respectively) [2]. A smaller study (n = 33)
ª The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

2. review Annals of Oncology
Table 1. Good prognosis typically ER-positive tumors component >50% of the lesion. The pure type contains mucin
in all of the IDC. The WHO classification divides this tumor
Dominant HER-2 Axillary lymph into three different subtypes: (i) mucinous carcinoma (ii)
profile node involvement % cystadenocarcinoma and columnar cell mucinous carcinoma
Tubular Negative 13–25 [2, 3] and (iii) signet ring cell carcinoma [1]. Pure mucinous
Invasive cribriform Negative 14.3 [4, 5] carcinomas represent 1%–4% of all breast cancers, with
Pure mucinous Negative £5 [6, 7] a reputation of presenting at one of the oldest median ages
Invasive solid papillary Negative 0 [8] (71 years). Despite often having a large tumor size, the axillary
Apocrine 50% £4 [9] lymph nodes are rarely involved; in a recent large series, 111
Solid neuroendocrinea Negative £40 (n = 8) [10] patients with mucinous breast cancer were identified. Ninety-
six (86%) patients underwent nodal evaluation either by
a
Does not differ from other carcinomas and depends very much on its sentinel lymph node biopsy or by axillary dissection. Fourteen
histological grade (see text). patients (13%) were found to have lymph node metastasis.
ER, estrogen receptor.
Node positivity was associated with larger tumor size (mean
2.7 cm). None of the 31 patients with tumor size <1 cm had
reported on 25% of the cases to involve axillary nodes, most known lymph node metastasis (24 were node negative, and
often micrometastases [3]. seven were not evaluated with sentinel lymph node biopsy or
diagnostic imaging. TC has a variety of presentations, but it is axillary dissection) [17]. In contrast to this study, there are
mostly seen on mammography as a small spiculated mass and reports on small tumors <1 cm presenting with at least a 5%
on sonography as an irregular mass with posterior acoustic incidence of nodal involvement [6, 7].
shadowing [11]. imaging. Pure mucinous carcinomas present an imaging
immunohistology. Most of the cases are ER (>90%) and challenge due to their isoechogenic appearance on ultrasound
progesterone receptor (PgR) positive with a low proliferation [18]. Typical magnetic resonance imaging (MRI) demonstrates
index. HER-2 status (as determined by immunohistochemical a gradually enhancing contrast pattern and a very high signal
staining or fluorescence in situ hybridization) and epidermal intensity on T2 images [19, 20].
growth factor receptor are negative [12]. immunohistology. These are mostly well-differentiated lesions
prognosis. Survival is not significantly different from that of the frequently associated with positive ERs (>90%) and PgRs (81.5%)
general population [13], even with positive axillary lymph nodes and HER-2-negative disease. However, rare cases with HER-2-
[14]. Five-year disease-free survival (DFS) for node-positive positive staining have been reported but these may need review.
patients was 94% (n = 64). Interestingly, in this series, the 5-year prognosis. Mucinous tumors have a favorable prognosis with
DFS of those who did not receive systemic treatment was 100%. 5-, 10-, 15- and 20-year survival rates of 94%, 89%, 85% and
81%, respectively [7]. Node involvement was associated with
invasive cribriform carcinoma a significant worse 5-year DFS or overall survival (OS) [13].
definition and epidemiology. These grade 1 tumors are Other traditional parameters such as age, T size, nuclear grade
characterized by a cribriform pattern in the majority of the and PgR status also significantly influence outcome [7].
invasive component. Tumors are divided into pure, classical
and mixed forms of invasive cribriform carcinoma (ICC). In invasive solid papillary carcinoma
the classical and the mixed forms, <50% of the tumor consists
definition and epidemiology. The literature is unclear whether
of other histological types [4]. This tumor accounts up to 3.5%
solid papillary carcinoma (SPC) is a form of in situ carcinoma
of the IEC, hence the data are based on case reports and small
or a true invasive malignancy and the WHO classification
series. The mean age is 53–58 years. Page et al. reported 14.3%
defines invasive SPC as a separate entity. SPC characteristically
of the cases to involve axillary lymph nodes [4, 5].
has papillae with focal solid areas. Ductal carcinoma in situ
diagnostic imaging. Stutz et al. reported on eight radiological (DCIS) is present in >75% of cases and lymphatic vessel
cases. Only four were seen on mammography and the invasion in one-third of the cases. The tumor comprises <1% to
ultrasound was not entirely typical of breast carcinoma [15]. 2% of IEC and typically presents in postmenopausal women
with only 15% of reported cases occurring under the age of 50.
immunohistology. ER is positive in 100% and PgR in 69% of the
Otsuki et al. reported on 20 patients with pure SPC and no
cases [5]; HER-2 is negative [16].
axillary lymph node involvement [8].
prognosis. In an older series, the 5-year survival was 100% for
pure and ‡50% ICC, 88% for <50% ICC and 78.3% for the IDC immunohistology. In total, 100% of the tumors are ER positive
controls [5]. Ten-year breast-specific survival for the pure cases and HER-2 negative and 80%–100% are PgR positive. Almost
was 100% [4]. all cases show positive staining for chromogranin and 40%
are also positive for synaptophysin [8, 21].
pure mucinous carcinoma imaging. The sonographic features are indistinguishable
definition and epidemiology. The mucinous neoplasms are from papillomas. The only differential finding between
characterized by the production of abundant extracellular and/ noninvasive and invasive papillary cancers was circumscribed
or intracellular mucin. The definition requires a mucinous margins [22].
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3. Annals of Oncology review
prognosis. Of the 1603 breast cancers reviewed in the National although we are cautious of this claim with the small number of
Surgical Adjuvant Breast and Bowel Project (NSABP)-04 study, cases reported.
35 had papillary features and only three experienced treatment
failure at 5 years [23]. Node-negative patients who had been
enrolled in the NSABP B-06 study revealed an improved survival
good prognosis, ER negative
after 10 years of follow-up compared with IDC-NOS [24]. Findings are summarized in Table 2.
apocrine carcinoma medullary carcinoma
definition and epidemiology. Microscopically, apocrine definition and epidemiology. This carcinoma is composed of
carcinomas (ACs) demonstrate the same architectural growth poorly differentiated cells with no glandular structures, scant
pattern as invasive ductal carcinomas of no special type, differing stroma, circumscribed margins and a prominent
only in their cytological appearance. The cells are characterized lymphoplasmacytic infiltrate. If most but not all the features are
by typical apocrine features with abundant eosinophilic granular present, the tumor is identified as ‘atypical medullary
cytoplasm and prominent/multiple nucleoli. There is no agreed carcinoma’ (AMC) [1]. Medullary carcinoma (MC) comprises
definition and some pathologists now confirm their diagnosis 1%–7% of IEC. In a large series of almost 1500 patients with
by staining for gross cystic disease fluid protein-15 [9, 25]. MC, only 27% had involved nodes. Although MC is not an
Axillary lymph node incidence varies from 1% to 4% but there indication for BRCA gene screening, there are growing data
is extremely sparse information in the literature. that indicate that MC may correlate with BRCA1 gene
mutation [30].
immunohistology. These tumors are reported as ER positive in
3.8%–60% of cases, PgR positive in 4.8%–40%, HER-2 positive diagnostic imaging. MC commonly manifests as well-
in 50%, with a proliferation index of 6.9%–23.7% and p53 circumscribed masses. Magnetic resonance mammography
alteration in 46%–50%. Androgen receptors are positive in appearance is nonspecific and often indicative of a benign
56%–100% of AC [9]. lesion [35, 36].
prognosis. AC has a similar prognosis to IDC-NOS when immunohistology. MC shares common characteristics with the
matched for stage and grade [26]. basal type breast cancer. Most of the tumors are hormone receptor
and HER-2 negative and CKT 5/6 positive (94%) [30, 37].
neuroendocrine tumors MC but not AMC lacks Bcl-2 and there are data that show
they differ in expression of human leukocyte antigen-DR, b2-
definition and epidemiology. Neuroendocrine (NE) was not
microglobulin, E cadherin and beta-catenin compared with
recognized as a single entity until the last WHO’s classification.
other tumors [38].
This classification differentiates between four different
subtypes: (i) small-cell carcinoma (SCC); (ii) large-cell prognosis. Paradoxical to its histology features, MC usually has
carcinoma; (iii) solid NE carcinoma; and (iv) atypical carcinoid a good prognosis. In one series, 10-year distant relapse-free
tumor. Our experience shows that the NE differentiation has survival reached 95% [30]. In another study, 10-year OS was 85%
no prognostic influence and on the whole they behave as per for MC as compared with 68% in the IDC-NOS patients [39].
their Nottingham grade [27]. Studies are hampered by lack of reproducibility of the
For simplification, this section describes the solid pathological diagnosis, small numbers of patients and poor
neuroendocrine subtype (SN) which represents a better statistical power.
prognosis group. (The SCC subtype is described in the ‘poor
prognosis, ER positive’ section.) The tumors consist of densely secretory breast carcinoma
cellular, solid nests and trabeculae of cells separated by delicate definition and epidemiology. Secretory breast carcinoma (SBC)
fibrovascular stroma [1]. Prevalence is up to 0.5% of breast is also known as juvenile carcinoma. This is an extremely rare
cancers. In a small series of eight patients, three presented with tumor with limited data available.
involved axillary lymph nodes. Two distinctive pathological characteristics of SBC are
immunohistology. As per the definition, there is synaptophysin intracellular/extracellular secretion and granular eosinophilic
or chromogranin immunohistochemical expression in 50% of cytoplasm of the neoplastic cells. Although secretory carcinoma
the cells. Typically, these tumors present with ER- and PgR- may occur in adults, the median and mean age are 33 and
positive and HER-2-negative status [10].
Table 2. Good prognosis typically ER-negative tumors
gene expression. Profile of endocrine carcinoma overlaps with
those of mucinous carcinomas [28]. Dominant HER-2 Axillary lymph
imaging. There is no specific imaging presentation in the profile node involvement %
limited number of SN tumors reported. Medullary Negative 27 [30]
Secretory Negative 15 [31]
prognosis. The outcome of these cancers does not differ from Adenoid cystic Negative 0–4.6 [32, 33]
other carcinomas and depends very much on its histological Acinic cell Negative 17 [34]
grade [27, 29]. The immunoprofile is reminiscent of the
luminal A subtypes, and hence a good prognosis is expected, ER, estrogen receptor.
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4. review Annals of Oncology
40 years, respectively. The literature mentions nodal and local recurrences were recorded. Larger series are required
involvement in 15% of the patients at presentation [31]. for definite conclusions [49].
imaging. SBC frequently appears as a small benign/intraductal
lesion on sonography [40]. poor prognosis, ER positive
immunohistochemistry. This subtype has the triple-negative Findings are summarized in Table 3.
phenotype (ER, PgR, and HER-2 negative). It has been
high-grade small-cell NE carcinoma
demonstrated that SCs of the breast consistently harbor the
t(12;15)ETV6-NTRK3 translocation [41]. The literature describes 40 cases of breast small cell NE
carcinoma (SCC) but this may be underreporting. This
prognosis. SBC has a favorable prognosis in children and neoplasm is similar to NE tumors presenting in the lung or
adolescents but seems slightly more aggressive in older patients. with extrapulmonary areas and share the same tumor markers.
Metastatic cases have been reported [1]. Diagnosis requires ruling out a nonmammary origin [53].
The presence of in situ component may be helpful but is not
adenoid cystic carcinoma essential [50, 54]. Most patients are in the sixth or seventh
definition and epidemiology. Adenoid cystic carcinomas (ACCs) decades of life and 59% present with involved lymph nodes.
are characterized by a mixture of proliferating glands, immunohistology. As per the definition, it expresses NE
myoepithelial cells and stromal/basement elements. Data in the markers, neurone-specific enolase, protein gene product 9.5,
literature are based on 200 cases. The tumor represents 0.1% chromogranin and synaptophysin, in 50% of the cell
of breast carcinoma and is diagnosed predominantly in population [1]. Most of the cases are positive for cytokeratin
postmenopausal women. Pain is a prominent symptom due to CAM5.2, AE1/3 and cytokeratin 7 as well. Surprisingly, the
neural involvement [42]. Most of the reports document a low tumor often expresses ERs and PgRs and this correlates with the
rate of axillary involvement of 0%–4.6%; however, there are degree of differentiation; well-differentiated tumors are the
some small series that report on up to 27% lymph node more likely to express hormone receptors with a varied
metastases [32, 33]. frequency of 0%–50%. Her-2 status is typically negative [55, 56].
immunohistochemistry. The tumor displays triple-negative imaging. Radiological findings are not specific but meet the
phenotype [43, 44]. However, a study with 28 patients found criteria for a suspicious mass [57].
46% of the cases to be ER positive and 36% to be PgR positive
[45]. In another study, all (n = 18) cases were c-kit (CD-117) prognosis. SCC tumor is considered an aggressive tumor with
positive. MIB-1 antibody (monoclonal antibody that is a poor prognosis. However, there are some reports about long-
immunoreactive with Ki-67) stains demonstrate low term survival when the diagnosis is made early [58]. NE
proliferative fraction [46]. differentiation using synaptophysin, chromogranin A, and
neuron-specific enolase had no prognostic influence [27].
prognosis. The 5-, 10- and 15-year OS rates were 85%–88%, 75%
and 60%, respectively, for ACC. Millar et al. reported an invasive micropapillary carcinoma
incidence of 26% (n = 5) for second malignancies at 15 years. definition and epidemiology. Hollow aggregates of malignant
The majority of the second cancers were not within the treated or cells and lymphatic invasion is a common feature of this tumor,
contralateral breast [33]. Metastases are rare and have been ranging from 72.3% to 91% of cases [51]. The pure variant is
reported to spread many years from diagnosis and without prior extremely rare. Mean age is 52.5 years (range 33–78). As
nodal disease [45, 47]. The most frequent site of metastases is opposed to the pure SPC, 70% of the patients present with
lung. Patients may live many years with metastases. involved axillary lymph nodes [51, 52].
acinic cell carcinoma immunohistochemistry. About two-thirds of the cases are ER
positive and up to 68% are PgR positive, one-third to one-half
definition and epidemiology. Acinic cell carcinoma is considered of the patients present with HER-2-positive status and 66%
as one of the types of salivary gland-like tumors of the breast with Bcl-2 positive. p53 overexpression was identified in 48% of
that show serous differentiation. Eighteen cases have been the cases [51, 59]. No basal-like immunostaining pattern was
reported in the literature. Ages range from 35 to 80 years. Three detected [60].
cases with positive lymph nodes are recorded [34].
imaging. Mammography is able to diagnose 80% of the cases.
imaging. A well-defined mass creates a differential diagnosis Masses appear with high density. The margins are commonly
with MC, intracystic carcinoma and metaplastic carcinoma [48].
Table 3. Poor prognosis typically ER-positive tumors
immunohistochemistry. This neoplasm is characterized by the
lack of ER, PgR and HER-2. Expression of markers such as
amylase, lysozyme and chymotrypsin is usually seen as in acinic Dominant HER-2 Axillary lymph
cells of the salivary glands. Stains positive for epithelial profile node involvement %
membrane antigen and S100 protein are frequently found. Small cell Negative 59 [50]
Invasive micropapillary £50% 70 [51, 52]
prognosis. The literature categorizes this tumor as a favorable
one; however, even within a short follow-up period, systemic ER, estrogen receptor.
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5. Annals of Oncology review
speculated; however, in approximately one-third of the lipid-rich carcinoma
patients, indistinct or microlobulated margins were seen. definition and epidemiology. This is defined as a tumor in which
Microcalcifications were present in 43.8% of patients. On 90% of its neoplastic cells contain abundant cytoplasmic
sonography, masses are typically hypoechoic, with only 60% of neutral lipids. Usually, it has very high-grade nuclear features
the masses showing posterior acoustic shadowing [61]. and poorly differentiated growth pattern. The tumor accounts
prognosis. Carcinoma with micropapillary features harbors for 1%–2% of all breast cancer with 84% of reported patients
a poor survival. The amount of IMC component correlates presenting at age £50. In one series, 80% were diagnosed with
strongly with the number of involved axillary lymph nodes. involved axillary lymph nodes and most had more than three
In the 5-year follow-up (range 4–199 months) of 98 positive lymph nodes. In total, 71% (35 of 49) were diagnosed
patients, 10-year OS was 48% and breast-specific survival with stage III disease. Many pathologists do not consider this
was 63.3%. The outcome of the patients did not differ type as a separate entity.
significantly from infiltrating ductal carcinomas of similar imaging. Although the tumors consist of a large proportion of
node status [62, 63]. lipid, they present with a higher density than adjacent tissue at
mammography.
poor prognosis, ERs negative immunohistochemistry. In the largest series (n = 49), 100% of
Findings are summarized in Table 4. the patients presented with ER-negative status. The vast
majority (90%) were PgR negative as well. Her-2
metaplastic carcinoma overexpression was found in 71.4% of this kind of neoplasm,
which was much higher than the 20% expected in the general
definition and epidemiology. This term is used for describing an
invasive breast carcinoma population. High Ki-67 proliferation
adenocarcinoma tumor with a dominant involvement of
activity was found in 55% of the cases.
a metaplastic component which may be of epithelial origin
such as squamous or adenocarcinoma with spindle cell prognosis. The 2- and 5-year OS rates were 64.6% and 33.2%,
differentiation or mesenchymal origin. Most of them are high respectively, with a median OS of 35 months. The only
grade [1]. Metaplastic carcinoma is usually diagnosed with T2 independent factor to predict survival was positive lymph
disease, with a mean size 3.4–4.4 cm and is commonly nodes [66]. In an earlier report, 38.5% of patients died in the
diagnosed in women 50 years of age. The incidence is 1% of first year following mastectomy [73].
all invasive breast carcinoma with a relative high proportion
of African American or Hispanic women (20%) [67, 68]. Most
studies report of a lower rate of axillary nodal involvement ‘unclassified’ due to lack of sufficient
than that is seen with IDC [64, 65]. information
imaging. No unique imaging features are found. glycogen-rich clear-cell carcinoma of the breast
Mammographically, either a circumscribed or an indistinct
definition and epidemiology. This is defined as carcinoma in
lesion is typical. On ultrasound, metaplastic carcinoma reveals
which 90% of the neoplastic cells have abundant clear
more benign features, characterized by oval, round or lobular
cytoplasm containing glycogen [1]. The incidence is 1.4%–3%
solid hypoechoic mass with circumscribed margins. On MRI,
of all breast cancers, presenting at a median age of 57. There is
almost all the cases show T2 hypersignal which is related to the
debate regarding this tumor’s behavior as some small series
necrotic component [69, 70].
report high axillary lymph nodal rate involvement of more than
immunohistology. Most of these high grade neoplasms show a 50% [53], whereas others report a much lower rate—35%
basal-like phenotype, few being positive for hormone receptors (n = 20) [74].
or HER-2 over-expression (0–8%) [69, 71].
imaging. There is not enough available data.
prognosis. These tumors have a high metastatic potential. More
immunohistology. In a series of 20 patients, 35% and 30% were
than 50% of these tumors are associated with local or distal
positive to ER and PgR, respectively. In total, 20% presented
recurrence. The spread is hematogenous rather than lymphatic.
with HER-2-positive status.
Hennessy et al. found a median OS of 37 months [72]. The
median survival from detection of metastatic disease was 8–12 prognosis. Fewer than 100 cases have been reported; thus, it
months [67, 69]. is difficult to draw definitive conclusions. Most authors
have found that this tumor has a poor prognosis but
there is no direct comparison to IDC-NOS based on stage
Table 4. Poor prognosis typically ER-negative tumors
[74, 75].
Dominant HER-2 Axillary lymph
profile % node involvement %
oncocytic carcinoma (malignant oncocytoma)
Metaplastic 0–8 20 [64, 65]
definition. The WHO classification requires 70% of the cells to
Lipid rich 71 80 [66] be oncocytic ones; however, only very few case reports are
published. Thus, we have found that no significant conclusion
ER, estrogen receptor. can be drawn.
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6. review Annals of Oncology
sebaceous carcinoma bud without jeopardizing local control and to avoid rib, lung
definition and epidemiology. This carcinoma is characterized by and other tissue damage. Thus, radiation may be omitted
a lobular or nested growth pattern of tumor cells variably according to some experts but again, there is only scanty data.
admixed with those displaying sebaceous differentiation. To As we cannot create systemic treatment algorithms using
our knowledge, only seven cases have been reported in the randomized trials with level one evidence due to the rarity of all
literature with ages ranging from 43 to 83 years. Sebaceous these tumors, can we use small case reports? Diab et al. found
tumor may precede internal malignancies and a genetic that axillary node involvement was a poor prognostic feature in
consultation to rule out Muir–Torre Syndrome should be mucinous carcinomas but not in TCs. Their conclusion was
considered. A case with involved lymph node at presentation that systemic adjuvant therapy and node dissection may be
was reported [76]. avoided in many patients with TC [13]. This conclusion is in
accordance with the recent knowledge regarding the lack of
immunohistochemistry. The hormone receptor status is sensitivity of luminal A breast cancers to chemotherapy and the
typically positive; however, two cases were reported to be role of endocrine treatments [83, 84]. However, further data
negative. No HER-2 overexpression was detected. In three are required before completely changing our guidelines for
analyzed cases, the percentage of Ki-67-positive tumor cells was these tumors.
relatively high and ranged from 16% to 38% [77]. ACC as a histological definition appears to have both
prognosis. Sebaceous carcinoma (SC) is generally felt to have prognostic and predictive significance by some authors as there
a worse prognosis than other cutaneous carcinomas. Due to are concerns regarding the sensitivity of this subtype to
the only scant published data, it is difficult to compare it with chemotherapy based mainly on the documented low response
the breast IDC-NOS. SC that had metastasized to the bone and rate in the head and neck adenoid cystic literature. There are
skin was reported .The case may imply on its aggressive data that this tumor has some response to chemotherapy drugs
potential [77, 78]. such as anthracyclines and 5-fluorouracil as well as more
modern agents such as paclitaxel [85, 86]. Large series,
however, are not available.
treatment data from the literature Recently, there has been interest in the platinum agents and
These epithelial tumors are far too rare to have been studied they have been incorporated into the arsenal of treatment of the
with specific randomized clinical trials to determine the triple-negative or basal subtypes. Several studies had shown
optimal surgical, radiation, chemotherapeutic or endocrine activity of these agents in the metastatic and neoadjuvant
treatment. Although occasionally these rare tumor types have treatment but larger studies are still pending. Knowing that
been included in large trials, the numbers are too small to draw phase III trial results for these rare types will not be
any conclusions regarding their response to treatment. In most forthcoming, can we make a leap and recommend platinum
situations, they have been treated with standard therapy as agent in the adjuvant setting for certain rare triple-negative
there are no data to indicate special protocols. subtypes such as metaplastic or the aggressive small-cell
Surgery is the first step of treatment of most of the early tumors? There is certainly rationale in administering adjuvant
breast cancers. The standard of care is lumpectomy/ cisplatin regimen in SCC breast cancer. This tumor has an
mastectomy with sentinel node biopsy (SNB). Many of the aggressive course and there are data showing a high rate of
special types such as tubular, cribriform, medullary and response in small-cell lung and extrapulmonary metastatic
mucinous have a low risk for regional involved lymph nodes disease. If NE breast cancers are just another extrapulmonary
but without more data, it is not clear whether SNB can be safely site of small-cell tumors, they may be treated in a similar
omitted. fashion but we do need to remember that for the adjuvant
Adjuvant radiation therapy has shown its benefit in breast breast cancer setting, this is not an evidence-based
cancer not only as a local control procedure but also as recommendation. For other types of these tumors, further
a treatment to prolong survival. ‘Favorable tumors’ tend to studies are necessary before treatment algorithms can
have lower rate of local and distant recurrences. When be created.
comparing IDC-NOS to medullary, tubular and mucinous
types, no statistically significant differences were found in the
local–regional failure rate among the four groups. In total, 31%
summary
of TCs and up to 37.5% of ACCs that had been treated with Rare epithelial breast cancers are a heterogeneous group of
excision only developed local recurrence [33, 47, 79]. malignancies with different behaviors and prognoses. Although
The significant parameters were still the traditional ones: histopathology has been our standard, there is now the
age, margins, lymphovascular invasion and extensive DCIS question of whether it is time to apply new technologies such as
[13, 39, 80]. microarrays and deep gene analysis to further understand these
Baker has stated that pure TC 1 cm in size could be treated rare tumors. Are they all really unique subtypes or not? Can
by excision only [81]. However, the NSABP B-20 trial that had they be classified according to their molecular or genetic
randomly assigned patients with small IDC tumors to yes/no features? Are the older histological subtypes of value in
adjuvant radiation could not find any subgroup which did not understanding the behavior of these rare tumors and are they
benefit from radiation therapy [82]. The secretory type which is really classifying specific tumors or not?
typically diagnosed in young girls represents a possible We have tried to classify these tumors with the data we have
exception since there is a strong effort to preserve the breast currently on ER status and outcome. These broad groups of
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7. Annals of Oncology review
estrogen-positive good outcome or poor outcome or similar 13. Diab SG, Clark GM, Osborne CK et al. Tumor characteristics and clinical outcome
estrogen-negative groups may be helpful in terms of of tubular and mucinous breast carcinomas. J Clin Oncol 1999; 17(5):
1442–1448.
conceptualizing where we are going but need further
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