25987109 tipos-infrecuentes-de-cancer-de-mama


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25987109 tipos-infrecuentes-de-cancer-de-mama

  1. 1. review Annals of Oncology 20: 1763–1770, 2009 doi:10.1093/annonc/mdp245 Published online 14 July 2009Breast carcinoma—rare types: review of the literatureR. Yerushalmi1*, M. M. Hayes2 & K. A. Gelmon11 Division of Medical Oncology and 2Department of Pathology, British Columbia Cancer Agency, Vancouver, British Columbia, CanadaReceived 23 February 2009; accepted 26 March 2009Invasive 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 HealthOrganization (WHO) classification. The rarity of many of these neoplasms does not allow large or randomized studiesto define the optimal treatment. Many of the descriptions of these cancers are from case reports and small series. Ourreview brings updated information on 16 epithelial subtypes as classified by the WHO system with a very concisehistopathology description and parameters helpful in the clinic. The aim of our review is to provide a tool for breastcancer caregivers which will enable a better understanding of the disease and its optimal approach to therapy. Thismay also stand as a clinical framework for a future understanding of these rarer breast cancers when gene analysis reviewwork is reported.Key words: breast carcinoma, epithelial breast cancer, prognosis, treatment, triple negative, World HealthOrganization classificationintroduction definition of breast cancer. The rarity of many of these neoplasms does not allow large or randomized studies to defineInvasive breast cancer is a heterogeneous disease in its the optimal treatment. Many of the descriptions of thesepresentation, 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 epithelialprincipally the terminal duct-lobular unit, and up to 75% of the subtypes as classified by the WHO system [1] with a verydiagnosed infiltrating ductal carcinoma are defined as invasive concise histopathology description and parameters helpful inductal carcinoma, not otherwise specified (IDC-NOS). The the clinic. The aim of our review is to provide a tool for breastsecond most common epithelial type is invasive lobular cancer caregivers which will enable a better understanding ofcarcinoma which comprises of 5%–15% of the group. the disease and its optimal approach to therapy. This may alsoHowever, there are more than a dozen variants which are less stand as a clinical framework for a future understanding ofcommon 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 theseclassifications are evolving as a standard part of the diagnosticprocess. This novel approach pushes aside traditional good prognosis, ER positivedescriptive definitions. An estrogen receptor (ER)-negativeductal (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 andthis may affect decision making for those less familiar with the tubular carcinomanuances of the rare tumor types. Furthermore, the classification definition and epidemiology. The definition of a tubularusing gene expression profile was established using a cohort of carcinoma (TC) requires tumor purity with 90% tubularductal carcinoma NOS, without including cancers of special architecture. The characteristic finding histologically is opentypes. We therefore indicate that it is extremely important to tubules composed of single layer of epithelial cells and cellularhighlight what is known about the different behavior of each desmoplastic stroma. Nuclear grade is low. TC comprises oftumor and gather together the published data with the goal of 0.7%–10.3% of the invasive epithelial breast cancer (IEC) and ismarrying 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 ColumbiaCancer 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. 2. review Annals of OncologyTable 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 carcinomaTubular Negative 13–25 [2, 3] and (iii) signet ring cell carcinoma [1]. Pure mucinousInvasive cribriform Negative 14.3 [4, 5] carcinomas represent 1%–4% of all breast cancers, withPure mucinous Negative £5 [6, 7] a reputation of presenting at one of the oldest median agesInvasive solid papillary Negative 0 [8] (71 years). Despite often having a large tumor size, the axillaryApocrine 50% £4 [9] lymph nodes are rarely involved; in a recent large series, 111Solid neuroendocrinea Negative £40 (n = 8) [10] patients with mucinous breast cancer were identified. Ninety- six (86%) patients underwent nodal evaluation either bya Does not differ from other carcinomas and depends very much on its sentinel lymph node biopsy or by axillary dissection. Fourteenhistological 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 hadreported on 25% of the cases to involve axillary nodes, most known lymph node metastasis (24 were node negative, andoften micrometastases [3]. seven were not evaluated with sentinel lymph node biopsy ordiagnostic imaging. TC has a variety of presentations, but it is axillary dissection) [17]. In contrast to this study, there aremostly 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 imagingimmunohistology. Most of the cases are ER (>90%) and challenge due to their isoechogenic appearance on ultrasoundprogesterone receptor (PgR) positive with a low proliferation [18]. Typical magnetic resonance imaging (MRI) demonstratesindex. HER-2 status (as determined by immunohistochemical a gradually enhancing contrast pattern and a very high signalstaining 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 lesionsprognosis. 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 withDFS 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 withinvasive 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 gradecharacterized by a cribriform pattern in the majority of the and PgR status also significantly influence outcome [7].invasive component. Tumors are divided into pure, classicaland mixed forms of invasive cribriform carcinoma (ICC). In invasive solid papillary carcinomathe classical and the mixed forms, <50% of the tumor consists definition and epidemiology. The literature is unclear whetherof other histological types [4]. This tumor accounts up to 3.5% solid papillary carcinoma (SPC) is a form of in situ carcinomaof the IEC, hence the data are based on case reports and small or a true invasive malignancy and the WHO classificationseries. The mean age is 53–58 years. Page et al. reported 14.3% defines invasive SPC as a separate entity. SPC characteristicallyof the cases to involve axillary lymph nodes [4, 5]. has papillae with focal solid areas. Ductal carcinoma in situdiagnostic imaging. Stutz et al. reported on eight radiological (DCIS) is present in >75% of cases and lymphatic vesselcases. Only four were seen on mammography and the invasion in one-third of the cases. The tumor comprises <1% toultrasound 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 nocases [5]; HER-2 is negative [16]. axillary lymph node involvement [8].prognosis. In an older series, the 5-year survival was 100% forpure and ‡50% ICC, 88% for <50% ICC and 78.3% for the IDC immunohistology. In total, 100% of the tumors are ER positivecontrols [5]. Ten-year breast-specific survival for the pure cases and HER-2 negative and 80%–100% are PgR positive. Almostwas 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 indistinguishabledefinition and epidemiology. The mucinous neoplasms are from papillomas. The only differential finding betweencharacterized by the production of abundant extracellular and/ noninvasive and invasive papillary cancers was circumscribedor intracellular mucin. The definition requires a mucinous margins [22].1764 | Yerushalmi et al. Volume 20 | No. 11 | November 2009
  3. 3. Annals of Oncology reviewprognosis. Of the 1603 breast cancers reviewed in the National although we are cautious of this claim with the small number ofSurgical Adjuvant Breast and Bowel Project (NSABP)-04 study, cases reported.35 had papillary features and only three experienced treatmentfailure at 5 years [23]. Node-negative patients who had beenenrolled in the NSABP B-06 study revealed an improved survival good prognosis, ER negativeafter 10 years of follow-up compared with IDC-NOS [24]. Findings are summarized in Table 2.apocrine carcinoma medullary carcinomadefinition and epidemiology. Microscopically, apocrine definition and epidemiology. This carcinoma is composed ofcarcinomas (ACs) demonstrate the same architectural growth poorly differentiated cells with no glandular structures, scantpattern as invasive ductal carcinomas of no special type, differing stroma, circumscribed margins and a prominentonly in their cytological appearance. The cells are characterized lymphoplasmacytic infiltrate. If most but not all the features areby typical apocrine features with abundant eosinophilic granular present, the tumor is identified as ‘atypical medullarycytoplasm and prominent/multiple nucleoli. There is no agreed carcinoma’ (AMC) [1]. Medullary carcinoma (MC) comprisesdefinition and some pathologists now confirm their diagnosis 1%–7% of IEC. In a large series of almost 1500 patients withby staining for gross cystic disease fluid protein-15 [9, 25]. MC, only 27% had involved nodes. Although MC is not anAxillary lymph node incidence varies from 1% to 4% but there indication for BRCA gene screening, there are growing datais 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 in3.8%–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 mammographyalteration in 46%–50%. Androgen receptors are positive in appearance is nonspecific and often indicative of a benign56%–100% of AC [9]. lesion [35, 36].prognosis. AC has a similar prognosis to IDC-NOS when immunohistology. MC shares common characteristics with thematched 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 withrecognized as a single entity until the last WHO’s classification. other tumors [38].This classification differentiates between four differentsubtypes: (i) small-cell carcinoma (SCC); (ii) large-cell prognosis. Paradoxical to its histology features, MC usually hascarcinoma; (iii) solid NE carcinoma; and (iv) atypical carcinoid a good prognosis. In one series, 10-year distant relapse-freetumor. 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 poorneuroendocrine subtype (SN) which represents a better statistical power.prognosis group. (The SCC subtype is described in the ‘poorprognosis, ER positive’ section.) The tumors consist of densely secretory breast carcinomacellular, 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 rarecancers. 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 areimmunohistology. As per the definition, there is synaptophysin intracellular/extracellular secretion and granular eosinophilicor chromogranin immunohistochemical expression in 50% of cytoplasm of the neoplastic cells. Although secretory carcinomathe cells. Typically, these tumors present with ER- and PgR- may occur in adults, the median and mean age are 33 andpositive and HER-2-negative status [10]. Table 2. Good prognosis typically ER-negative tumorsgene expression. Profile of endocrine carcinoma overlaps withthose of mucinous carcinomas [28]. Dominant HER-2 Axillary lymphimaging. 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 theluminal A subtypes, and hence a good prognosis is expected, ER, estrogen receptor.Volume 20 | No. 11 | November 2009 doi:10.1093/annonc/mdp245 | 1765
  4. 4. review Annals of Oncology40 years, respectively. The literature mentions nodal and local recurrences were recorded. Larger series are requiredinvolvement in 15% of the patients at presentation [31]. for definite conclusions [49].imaging. SBC frequently appears as a small benign/intraductallesion on sonography [40]. poor prognosis, ER positiveimmunohistochemistry. 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 carcinomademonstrated that SCs of the breast consistently harbor thet(12;15)ETV6-NTRK3 translocation [41]. The literature describes 40 cases of breast small cell NE carcinoma (SCC) but this may be underreporting. Thisprognosis. SBC has a favorable prognosis in children and neoplasm is similar to NE tumors presenting in the lung oradolescents 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 notadenoid cystic carcinoma essential [50, 54]. Most patients are in the sixth or seventhdefinition 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 NEmyoepithelial 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 cellof breast carcinoma and is diagnosed predominantly in population [1]. Most of the cases are positive for cytokeratinpostmenopausal women. Pain is a prominent symptom due to CAM5.2, AE1/3 and cytokeratin 7 as well. Surprisingly, theneural involvement [42]. Most of the reports document a low tumor often expresses ERs and PgRs and this correlates with therate of axillary involvement of 0%–4.6%; however, there are degree of differentiation; well-differentiated tumors are thesome small series that report on up to 27% lymph node more likely to express hormone receptors with a variedmetastases [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 thephenotype [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 withpositive. 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]. NEproliferative 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 carcinomaincidence of 26% (n = 5) for second malignancies at 15 years. definition and epidemiology. Hollow aggregates of malignantThe 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 isreported to spread many years from diagnosis and without prior extremely rare. Mean age is 52.5 years (range 33–78). Asnodal disease [45, 47]. The most frequent site of metastases is opposed to the pure SPC, 70% of the patients present withlung. 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-halfdefinition 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% ofthat show serous differentiation. Eighteen cases have been the cases [51, 59]. No basal-like immunostaining pattern wasreported 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 commonlywith MC, intracystic carcinoma and metaplastic carcinoma [48]. Table 3. Poor prognosis typically ER-positive tumorsimmunohistochemistry. This neoplasm is characterized by thelack of ER, PgR and HER-2. Expression of markers such asamylase, lysozyme and chymotrypsin is usually seen as in acinic Dominant HER-2 Axillary lymphcells 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 favorableone; however, even within a short follow-up period, systemic ER, estrogen receptor.1766 | Yerushalmi et al. Volume 20 | No. 11 | November 2009
  5. 5. Annals of Oncology reviewspeculated; however, in approximately one-third of the lipid-rich carcinomapatients, indistinct or microlobulated margins were seen. definition and epidemiology. This is defined as a tumor in whichMicrocalcifications were present in 43.8% of patients. On 90% of its neoplastic cells contain abundant cytoplasmicsonography, masses are typically hypoechoic, with only 60% of neutral lipids. Usually, it has very high-grade nuclear featuresthe masses showing posterior acoustic shadowing [61]. and poorly differentiated growth pattern. The tumor accountsprognosis. Carcinoma with micropapillary features harbors for 1%–2% of all breast cancer with 84% of reported patientsa poor survival. The amount of IMC component correlates presenting at age £50. In one series, 80% were diagnosed withstrongly 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 diagnosedpatients, 10-year OS was 48% and breast-specific survival with stage III disease. Many pathologists do not consider thiswas 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 ofnode 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% ofFindings are summarized in Table 4. the patients presented with ER-negative status. The vast majority (90%) were PgR negative as well. Her-2metaplastic carcinoma overexpression was found in 71.4% of this kind of neoplasm, which was much higher than the 20% expected in the generaldefinition and epidemiology. This term is used for describing an invasive breast carcinoma population. High Ki-67 proliferationadenocarcinoma tumor with a dominant involvement of activity was found in 55% of the cases.a metaplastic component which may be of epithelial originsuch 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 onlygrade [1]. Metaplastic carcinoma is usually diagnosed with T2 independent factor to predict survival was positive lymphdisease, with a mean size 3.4–4.4 cm and is commonly nodes [66]. In an earlier report, 38.5% of patients died in thediagnosed in women 50 years of age. The incidence is 1% of first year following mastectomy [73].all invasive breast carcinoma with a relative high proportionof African American or Hispanic women (20%) [67, 68]. Moststudies report of a lower rate of axillary nodal involvement ‘unclassified’ due to lack of sufficientthan that is seen with IDC [64, 65]. informationimaging. No unique imaging features are found. glycogen-rich clear-cell carcinoma of the breastMammographically, either a circumscribed or an indistinct definition and epidemiology. This is defined as carcinoma inlesion is typical. On ultrasound, metaplastic carcinoma reveals which 90% of the neoplastic cells have abundant clearmore 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 isalmost all the cases show T2 hypersignal which is related to the debate regarding this tumor’s behavior as some small seriesnecrotic component [69, 70]. report high axillary lymph nodal rate involvement of more thanimmunohistology. 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% werethan 50% of these tumors are associated with local or distal positive to ER and PgR, respectively. In total, 20% presentedrecurrence. The spread is hematogenous rather than lymphatic. with HER-2-positive status.Hennessy et al. found a median OS of 37 months [72]. Themedian survival from detection of metastatic disease was 8–12 prognosis. Fewer than 100 cases have been reported; thus, itmonths [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 stageTable 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 toLipid rich 71 80 [66] be oncocytic ones; however, only very few case reports are published. Thus, we have found that no significant conclusionER, estrogen receptor. can be drawn.Volume 20 | No. 11 | November 2009 doi:10.1093/annonc/mdp245 | 1767
  6. 6. review Annals of Oncologysebaceous carcinoma bud without jeopardizing local control and to avoid rib, lungdefinition and epidemiology. This carcinoma is characterized by and other tissue damage. Thus, radiation may be omitteda 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 usingour knowledge, only seven cases have been reported in the randomized trials with level one evidence due to the rarity of allliterature with ages ranging from 43 to 83 years. Sebaceous these tumors, can we use small case reports? Diab et al. foundtumor may precede internal malignancies and a genetic that axillary node involvement was a poor prognostic feature inconsultation to rule out Muir–Torre Syndrome should be mucinous carcinomas but not in TCs. Their conclusion wasconsidered. A case with involved lymph node at presentation that systemic adjuvant therapy and node dissection may bewas reported [76]. avoided in many patients with TC [13]. This conclusion is in accordance with the recent knowledge regarding the lack ofimmunohistochemistry. The hormone receptor status is sensitivity of luminal A breast cancers to chemotherapy and thetypically positive; however, two cases were reported to be role of endocrine treatments [83, 84]. However, further datanegative. No HER-2 overexpression was detected. In three are required before completely changing our guidelines foranalyzed 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 bothprognosis. Sebaceous carcinoma (SC) is generally felt to have prognostic and predictive significance by some authors as therea worse prognosis than other cutaneous carcinomas. Due to are concerns regarding the sensitivity of this subtype tothe only scant published data, it is difficult to compare it with chemotherapy based mainly on the documented low responsethe breast IDC-NOS. SC that had metastasized to the bone and rate in the head and neck adenoid cystic literature. There areskin was reported .The case may imply on its aggressive data that this tumor has some response to chemotherapy drugspotential [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 andThese epithelial tumors are far too rare to have been studied they have been incorporated into the arsenal of treatment of thewith specific randomized clinical trials to determine the triple-negative or basal subtypes. Several studies had shownoptimal surgical, radiation, chemotherapeutic or endocrine activity of these agents in the metastatic and neoadjuvanttreatment. Although occasionally these rare tumor types have treatment but larger studies are still pending. Knowing thatbeen included in large trials, the numbers are too small to draw phase III trial results for these rare types will not beany conclusions regarding their response to treatment. In most forthcoming, can we make a leap and recommend platinumsituations, they have been treated with standard therapy as agent in the adjuvant setting for certain rare triple-negativethere 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 adjuvantbreast cancers. The standard of care is lumpectomy/ cisplatin regimen in SCC breast cancer. This tumor has anmastectomy with sentinel node biopsy (SNB). Many of the aggressive course and there are data showing a high rate ofspecial types such as tubular, cribriform, medullary and response in small-cell lung and extrapulmonary metastaticmucinous have a low risk for regional involved lymph nodes disease. If NE breast cancers are just another extrapulmonarybut without more data, it is not clear whether SNB can be safely site of small-cell tumors, they may be treated in a similaromitted. 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-basedcancer not only as a local control procedure but also as recommendation. For other types of these tumors, furthera treatment to prolong survival. ‘Favorable tumors’ tend to studies are necessary before treatment algorithms canhave lower rate of local and distant recurrences. When be created.comparing IDC-NOS to medullary, tubular and mucinoustypes, no statistically significant differences were found in thelocal–regional failure rate among the four groups. In total, 31% summaryof TCs and up to 37.5% of ACCs that had been treated with Rare epithelial breast cancers are a heterogeneous group ofexcision 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 theage, 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? Canby excision only [81]. However, the NSABP B-20 trial that had they be classified according to their molecular or geneticrandomly assigned patients with small IDC tumors to yes/no features? Are the older histological subtypes of value inadjuvant radiation could not find any subgroup which did not understanding the behavior of these rare tumors and are theybenefit 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 haveexception since there is a strong effort to preserve the breast currently on ER status and outcome. These broad groups of1768 | Yerushalmi et al. Volume 20 | No. 11 | November 2009
  7. 7. Annals of Oncology reviewestrogen-positive good outcome or poor outcome or similar 13. Diab SG, Clark GM, Osborne CK et al. Tumor characteristics and clinical outcomeestrogen-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 furtherassessment. As well, the poor prognosis of some of these 14. Cabral AH, Recine M, Paramo JC et al. Tubular carcinoma of the breast: an institutional experience and review of the literature. Breast J 2003; 9(4):subtypes reflects the need for a better adjuvant treatment and 298–301.an understanding of these specific groups based on both their 15. Stutz JA, Evans AJ, Pinder S et al. The radiological appearances of invasivehistological appearance and their molecular staining. cribriform carcinoma of the breast. Nottingham Breast Team. Clin Radiol 1994; We are proposing and organizing a consortium of 49(10): 693–695.investigators from around the world to gather a sizable number 16. Soomro S, Shousha S, Taylor P et al. c-erbB-2 expression in different histologicalof these rare tumor types, assess the tumors centrally by types of invasive breast carcinoma. J Clin Pathol 1991; 44(3): 211–214.modern array technology and try to group these with outcome 17. Barkley CR, Ligibel JA, Wong JS et al. Mucinous breast carcinoma: a largeand treatment data. This has been established for the common contemporary series. Am J Surg 2008; 196(4): 549–551.tumors and we have many leads as to their subclassification 18. Memis A, Ozdemir N, Parildar M et al. Mucinous (colloid) breast cancer:but a further analysis of these rare tumors is also needed. This mammographic and US features with histologic correlation. Eur J Radiol 2000;exercise may provide the necessary information to begin to 35(1): 39–43.further understand the behavior of these tumors and to begin 19. Kawashima M, Tamaki Y, Nonaka T et al. MR imaging of mucinous carcinoma of the breast. AJR Am J Roentgenol 2002; 179(1): 179–183.to classify them according to their relevant features. 20. Okafuji T, Yabuuchi H, Sakai S et al. MR imaging features of pure mucinousSubsequently, there may be a role for trials using carcinoma of the breast. Eur J Radiol 2006; 60(3): 405–413.a contemporary classification to look at uniform treatment 21. Reiner A, Reiner G, Spona J et al. Histopathologic characterization of humanmodalities and begin to establish treatment algorithms and breast cancer in correlation with estrogen receptor status. A comparison ofguidelines. Until such time, we believe broad classifications into immunocytochemical and biochemical analysis. 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