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Academic Department of Gynaecological Oncology, Mauriziano Umberto I° Hospital of Turin and Institute for Cancer Research and Treatment of Candiolo, University of Turin, Largo Turati 62, 10129 Turin, Italy
(Correspondence should be addressed to N Biglia; Email: nbiglia{at}mauriziano.it)
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Abstract |
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 Top Abstract IntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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Introduction |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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Epidemiology |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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). As a result, the proportion of all breast tumours with a lobular component rose from 9.5% in 1987 to 15.6% in 1999 (Li et al. 2003a). The incidence rates of ILC and IDLC increased mainly in postmenopausal women during 50–59 years of age, although these increases were evident throughout the overall age range (Li et al. 2003a; Table 2).
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HRT and breast carcinoma |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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The impact of HRT on breast cancer risk seems to be different depending on histological type.
Six recent studies have reported that ever and current use of HRT is associated with a significant increased risk for the development of ILC, but has little impact on the risk of IDC (Li et al. 2000b, 2003c, Chen et al. 2002, Daling et al. 2002, Newcomb et al. 2002, Newcomer et al. 2003; Table 3). The three studies that evaluated duration of use showed that ILC risk increased as duration of HRT use increased (Chen et al. 2002, Daling et al. 2002, Li et al. 2003c). However, some of these reports have been limited by small numbers of women with lobular cancer, and none has been able to assess the possible impact of very long duration HRT (i.e. > 15 years). In a recent analysis of the Million Women Study, the relative risks of invasive breast cancer in current users when compared with never users of HRT varied significantly according to tumour histology. The relative risks in current when compared with never users of HRT were 2.25 (95% CI 2.0–2.52) for lobular and 2.13 (95% CI 1.68–2.70) for mixed ductal–lobular (Reeves et al. 2006). Also in our series the incidence of ILC was significantly higher in HRT ever users (i.e. 
6 months) when compared with never users (Biglia et al. 2005). In two out of the six studies, risk of breast cancer by different regimens (sequential or continuous combined) of HRT use was reported (Chen et al. 2002, Daling et al. 2002). In one study, it was found that sequential and continuous combined HRT use were both associated with an increased risk of ILC (Chen et al. 2002), while in the other study, only continuous HRT was associated with an increased risk of ILC (Daling et al. 2002). In these studies, the use of ERT was not significantly associated with an increased risk of breast carcinoma for any of the histological groups (Li et al. 2000b, 2003c Chen et al. 2002, Daling et al. 2002, Newcomb et al. 2002, Newcomer et al. 2003). For instance, Li et al. (2003c) have reported that women using ERT, even for 25 years or longer, have no appreciable increase in risk of breast cancer, although the associated odds ratios are not inconsistent with a possible small effect.
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Lobular cancers |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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Diagnosis of invasive lobular cancer |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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Clinical examination of patients with ILC can be complicated because of vague findings, such as thickening or induration, which are often the only clinical signs, particularly in early disease (Evans et al. 2002).
Mammography
The sensitivity of detecting ILC has been reported to be as low as 57–76% for Mx (Le Gal et al. 1992, Evans et al. 2002), while false negative rates at Mx have been observed to range from 8 to 24% (Helvie et al. 1993, Krecke & Gisvold 1993). In the study by Krecke & Gisvold (1993) the mammograms of patients with ILC initially classified as normal (i.e. false negative) were reviewed after surgery and in almost 50% of the cases the radiologists failed to detect any radiological alteration. Similarly, in a recent analysis, two radiologists retrospectively evaluating preoperative mammograms of 42 ILC found that 35–37% of the cases were under-staged (Veltman et al. 2006). The result of the particular growing pattern of ILC is that a discrete mass with the mammographic appearance of stellate opacity is less common than that observed with other breast malignancies (Evans et al. 2002). ILC is associated with a higher incidence of asymmetric density (3–25%) or architectural distortion (10–28%) and is often less radiopaque than normal fibroglandular tissue (Mendelson et al. 1989, Watson 2001). Microcalcifications have been reported only in 1–28% of cases, and frequently represent unrelated histological lesions such as IDC, ductal carcinoma in situ and sclerosing adenosis (Mendelson et al. 1989, Helvie et al. 1993, Krecke & Gisvold 1993). In a series of 94 ILCs assessed with Mx, 60% of these lesions manifested as masses, of which 71% were described as irregular and spiculated; 21% as architectural distortions; and the remaining 20% as either asymmetric densities or calcifications (Evans et al. 2002). More recently Boetes et al.(2004) showed that a mass was visible on Mx only in 58% of the women, while an architectural distortion was present in 28%. A large proportion of ILCs have been found to be visible in one view only, most often the craniocaudal view (Cornford et al. 1995).
Ultrasound
The sensitivity of US for the detection of ILC has been reported to range between 25 and 88% (Paramagul et al. 1995, Rissanen et al. 1998). Some authors found that US significantly improves the detection of ILC in patients presenting with palpable nodules and no mammographically identified masses (Butler et al. 1999, Evans & Lyons 2000). Others reported that US has a limited role in ILC because of the variety of US appearances and a very low sensitivity and specificity for the diagnosis of small tumours (Chintana et al. 1995). However, a high detection rate by US, sensitivity of 87.7%, was also found in a series of 81 mammographically subtle or invisible ILCs, although most of them were not clinically palpable (Butler et al. 1999). The prediction of breast cancer size by US and Mx is less accurate in lobular than ductal carcinoma (Golshan et al. 2004). Moreover, US correlation with pathology has been shown to become less accurate as tumour size increases (Tresserra et al. 1999).
Magnetic resonance imaging
Further diagnostic difficulties may derive from the higher rates of multifocal and/or multicentric tumours when compared with ductal carcinoma and the associated higher incidence of synchronous and/or metachronous controlateral disease, typical of lobular histology (Cornford et al. 1995, Sastre-Garau et al. 1996, Toikkanen et al. 1997, Korhonen et al. 2004). Several studies have demonstrated that MRI detects additional malignancy occult on Mx and separate from the primary tumour site or in the controlateral breast in 16–58% of patients with ILC (Rodenko et al. 1996, Esserman et al. 2002, Kneeshaw et al. 2003, Quan et al. 2003, Boetes et al. 2004). Rodenko et al.(1996) compared 20 mastectomy specimens of ILC serially sectioned in a sagittal plane with the preoperative MRI sagittal images, showing a highly significant correlation between MRI and pathology, with 85% agreement by size and location of multifocal/multi-centric lesions, when compared with 27–36% obtained with Mx alone. It was also noted that MRI was able to detect unsuspected skin extension not seen by Mx, whereas it appeared to overestimate the presence of chest-wall invasion (Rodenko et al. 1996). This high sensitivity of MRI has been demonstrated to affect remarkably the management of ILC, often producing variations in the surgical planning. In a large study on 463 women, Fischer et al. reported a change in management of 14.3% of the patients with ILCs following MRI due to the presence of more extensive disease (Fisher et al. 1999). In a series of 267 patients with primary breast tumours, patients with lobular histology were twice as likely to experience a change in therapy based on improved MRI staging when compared with patients who had all other histological subtypes (Bedrosian et al. 2003). The majority of these patients with ILCs were converted to mastectomy and MRI suspicion of malignancy was validated pathologically in 82% of the cases (Bedrosian et al. 2003).
Fine needle aspiration
The reported false negative rate in fine needle aspiration (FNA) of ILC ranges from 15% to ~60% with a sensitivity of 60.5–76%, considerably lower than that of IDCs (Schelfout et al. 2004). A false negative core biopsy is also more likely because of the difficult in the localization of the lesions and the sparse cellularity of the tumour (Pointon & Cunningham 1999). The lower sensitivity of FNA in ILC appears to be due to sampling and interpretative errors, caused by tumour specific factors such as the characteristic low-grade atypia, the small-sized cells and the histological type of ILC (classic versus non-classic; Hwang et al. 2004, Molland et al. 2004). The cytologic cellularity of the lesion does not reflect the actual cellularity of the tumour, but instead is an indicator of the architectural arrangement of the neoplastic cells. Tumours that form epithelial cell groups, such as in non-classic ILC, tend to yield more cellular aspirates that are diagnostic for carcinoma. In contrast, classic ILC, in which single neoplastic cells are embedded in fibrous stroma, is more likely to yield a paucicellular smear with subtle atypia and rare single intact epithelial cells (Hwang et al. 2002).
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Biological and clinical features of invasive lobular cancer |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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).
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ILC occurs more frequently in older patients and is larger in size than IDC (Sastre-Garau et al. 1996, Mersin et al. 2003, Arpino et al. 2004). The older age at diagnosis of patients with ILC may be due to a low proliferative rate or greater difficulties in detecting ILC. These diagnostic difficulties may also account for the higher incidence of ILCs reported in patients with initially metastatic breast carcinoma (Jimeno et al. 2004). Despite the larger size of ILC, it has been observed that the rate of lymph nodal involvement is the same or even slightly lower when compared with IDC (Mersin et al. 2003, Arpino et al. 2004, Korhonen et al. 2004).
Several studies have shown that ILC is frequently C-ErbB-2 negative, bcl-2 positive and p53 negative (Frolik et al. 2001, Coradini et al. 2002, Cocquyt et al. 2003, Arpino et al. 2004, Korhonen et al. 2004, Mathieu et al. 2004; Table 5). In addition, the proliferative activity and lymphatic-vascular invasion rate are lower in ILC and VEGF is more frequently under-expressed, thus suggesting that ILC has more favourable biological features when compared with IDC (Frolik et al. 2001, Coradini et al. 2002, Mersin et al. 2003, Arpino et al. 2004, Mathieu et al. 2004, Molland et al. 2004; Table 5).
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The aggressive behaviour and the consequent poor prognosis of pleomorphic lobular carcinoma, reported in many series, have been attributed to the more frequent overexpression of HER2 and the generally low apoptosis rate. Moreover, the pleomorphic appearance of this variant hinders its correct identification and differentiation from ductal carcinoma (Frolik et al. 2001).
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Surgical treatment of invasive lobular cancer |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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The clinicopathological features of ILC and the higher rates of multifocal and multicentric lesions when compared with IDC, ranging from 4.5 to 31%, had led to questioning the effectiveness of breast-conservative surgery (BCS; Sastre-Garau et al. 1996, Toikkanen et al. 1997, Hussien et al. 2003). The suggestion for mastectomy as a safer option to control local disease in patients with ILC was based on the higher local recurrence rates after BCS when compared with IDC reported in some old series (Mate et al. 1986). Many other authors were not able to confirm this difference (Kurtz et al. 1989, Schnitt et al. 1989, Poen et al. 1992, Weiss et al. 1992, Silverstein et al. 1994, White et al. 1994, Sastre-Garau et al. 1996, Bouvet et al. 1997, Haffty et al. 1997, Salvadori et al. 1997, Peiro et al. 2000, Molland et al. 2004, Santiago et al. 2005, Vo et al. 2006; Table 6). Several factors have been demonstrated to affect local recurrence after BCS and it is generally recognized that positive margins are one of the most important determinants of local recurrence (Hussien et al. 2003, Chagpar et al. 2004, Horst et al. 2005). The histological subtype has been found to affect margin status in some reports (Mai et al. 2000, Park et al. 2000), but not in others (Horiguchi et al. 1999). A large study on 2658 patients treated with lumpectomy has confirmed that patients with lobular histology are at higher risk for positive margins and, therefore, may require a wider initial resection (Chagpar et al. 2004). The insidious histological growth pattern of ILC with malignant cells infiltrating singly or in small clusters the normal breast makes the gross extent of disease difficult to define at operation (Chagpar et al. 2004, Fleming et al. 2004). Fleming et al. have recently reported a significant difference between the median macroscopic (20 mm) and the median microscopic (25 mm) tumour size in patients with ILC. Moreover, the macroscopic intraoperative margin assessment was less successful in ILC with a sensitivity and specificity of 0.6 and 0.83 respectively when compared with IDC sensitivity of 0.8 and a specificity of 0.93 (Fleming et al. 2004).
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At present, only few studies have compared BCS and mastectomy in patients with ILC (Du Toit et al. 1991, Holland et al. 1995, Warneke et al. 1996, Chung et al. 1997, Hussien et al. 2003, Singletary et al. 2005; Table 7). Most authors have concluded that ILC can be safely treated with BCS with no difference in local recurrence (Holland et al. 1995, Warneke et al. 1996, Chung et al. 1997). Furthermore, the two studies that have found a significant increase of local recurrence rates in patients with ILC after BCS should hardly be taken into account because of the inexplicably high recurrence rates of about 40% (Du Toit et al. 1991, Hussien et al. 2003).
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The reported incidence rate of controlateral ILC varies from 2.7 to 23% (Du Toit et al. 1991, Sastre-Garau et al. 1996, Arpino et al. 2004). For this reason the management of controlateral breast cancer risk in patients diagnosed with ILC is still controversial and have ranged from prophylactic mastectomy to random controlateral breast biopsy to follow-up with investigation of any suspicious lesion (Lee et al. 1995). Nevertheless, a careful pre- and post-operative assessment of the controlateral breast in patients with ILC is mandatory, especially in the light of more recent data. Polednak has assessed 300 patients with bilateral synchronous breast carcinoma (BSBC) and 13 495 patients with unilateral breast carcinoma recorded between 1995 and 1999 at the Connecticut Tumour Registry. Lobular histology was significantly more frequent in BSBC patients and, although length of follow-up was limited, the risk of death was higher in BSBC (RR: 1.43, P < 0.05) than in unilateral patients (Polednak 2003). In a retrospective review of 239 patients with unilateral early stage breast carcinoma who underwent controlateral prophylactic mastectomy, ILC in the index breast was a major determinant of controlateral breast tumours (Goldflam et al. 2004).
Sentinel lymph node biopsy feasibility and accuracy of intraoperative assessment
The presence of axillary lymph node metastases is the most significant prognostic factor for patients with early stage breast cancer. The specific nature of ILC, as difficult to detect and often multifocal and/or multi-centric, has brought into question the feasibility of nodal staging with sentinel node biopsy (SNB). Moreover, because ILC usually has low mitotic rate with uniform appearance of bland tumour cells that lack cellular atypia, and tends to infiltrate lymph nodes in a single cell pattern, the distinction between lobular carcinoma cells and lymphoid cells can be extremely challenging (Cocquyt & Van Belle 2005). Therefore, particular attention should be given to histological specimens of lobular carcinomas because nodal metastases are more often missed with ILC, and false negative results are more frequently reported when compared with ductal carcinomas (Cocquyt & Van Belle 2005). Old studies have excluded patients with multifocal breast tumour on the assumption that tumours located in different breast quadrants drain to different sentinel lymph nodes and, therefore, SNB would result in inaccurate axillary lymph node staging. Conversely, different techniques adopting subareolar and peritumoural injection sites have demonstrated the identification of the same sentinel node, thus suggesting that the drainage of the different quadrants of the breast have a final common lymphatic pathway to the axilla (Tuttle et al. 2002). A recent analysis of 75 patients with multifocal tumours and 559 patients with unifocal tumours did not show any difference in the false negative rate, overall accuracy and negative predictive value of the SNB technique between the multifocal and the unifocal groups (Goyal et al. 2004).
A prospective study have compared the detection rates and false negative rates in patients with ILC and IDC of SNB; the false negative rate was 7.6% for IDC and 9% for ILC (Classe et al. 2004).
Creager et al. have evaluated the intraoperative imprint cytology of sentinel lymph nodes for ILC. The sensitivity of this technique for ILC was 52%, the specificity 100% and the accuracy 82%. Compared with IDC, these parameters were not significantly different. However, the sensitivity for detecting micrometastasis of ILC was only 25% (Creager & Geisinger 2002). Hence, if micrometastases are used to determine the need for further axillary dissection, more sensitive intraoperative tools will be necessary to avoid a second surgical intervention. Despite these limitations, SNB can be considered a valuable and accurate technique to stage the axilla in ILC.
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Preoperative chemotherapy (PCT) in invasive lobular cancer |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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Clinical and pathological responses to PCT are less frequent in ILC compared with IDC (Cocquyt et al. 2003, Mathieu et al. 2004, Cristofanilli et al. 2005, Tubiana-Hulin et al. 2006; Table 8). In a recent study, the difference in pathological response rates between ILC and IDC persists even after adjusting for hormone receptor status and use of taxanes (Cristofanilli et al. 2005). Cocquyt et al. have assessed responses to primary chemotherapy in 135 patients with breast tumours larger than 3 cm on clinical examination. Overall clinical and pathological response were significantly higher in IDC, when compared with ILC (75 vs 50%, P = 0.0151) and the type of PCT did not affect this result. The estimated odds of having a response were approximately three times higher for patients with IDC than for patients with ILC (Cocquyt et al. 2003). Consistent with these findings, Mathieu et al.(2004) reported that clinical response to PCT was lower for ILC when compared with IDC (26 vs 58%, P = 0.001) and none of the 38 patients diagnosed with ILC had a complete pathological response after PCT (Table 8).
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Prognosis of patients with invasive lobular cancer |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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The 5-year OS and disease-free survival (DFS) rates for patients with ILC ranges from 68 to 87% and 73 to 98% respectively (Silverstein et al. 1994, Sastre-Garau et al. 1996). This variability might be due to the discrepancy in the histological criteria used to define ILC, to the relatively small numbers of patients and to differences in the adjuvant therapies used across the studies (Cristofanilli et al. 2005).
Intuitively, the more favourable prognostic factors of ILC would translate into a survival advantage for patients with ILC. Nonetheless, many studies have shown that the survival rates are not significantly different in ILC and IDC and only in few old studies ILC has statistically significant better OS and DFS than IDC (Silverstein et al. 1994, Toikkanen et al. 1997, Winchester et al. 1998, Mersin et al. 2003, Arpino et al. 2004, Korhonen et al. 2004, Molland et al. 2004, Ugnat et al. 2004, Santiago et al. 2005; Table 9).
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In a retrospective cohort study on 164 958 women diagnosed with breast cancer in the SEER cancer registries from 1974 to 1998, lobular tumours were associated with a risk of mortality 11% lower than IDC. The magnitude of this lower risk increased over time, as ILC was associated with an 8% lower risk of mortality when compared with IDC between 1974 and 1983, and a 24% lower risk between 1994 and 1998 (Li et al. 2003d). The authors recognized that a limitation of this study was the lack of data concerning the adjuvant hormonal therapy. In fact, lobular tumours are more likely than ductal tumours to be hormone receptor-positive and, therefore, are suitable candidates for hormonal treatment with tamoxifen, which is known to reduce mortality. Hence, the risk of mortality associated with ILC may have decreased as tamoxifen use is increased over the study period (Li et al. 2003d). Similarly, the considerable survival after recurrence reported in some series has been explained by a better response to hormonal treatments of patients with ILC (Arpino et al. 2004, Korhonen et al. 2004). This favourable prognostic impact of ILC has also been confirmed by the 5-year survival analysis conducted on a sample of 4478 breast cancer patients; the RR of death was 0.58 (95% CI 0.37–0.91) for lobular tumours as compared with IDC (Allemani et al. 2004). Conversely, histology failed to achieve significant independent prognostic information in other series (Ugnat et al. 2004, Tubiana-Hulin et al. 2006). Nonetheless, in the 5-year survival analysis of 2192 patients with primary breast cancer registered by the ORCC (OR Cancer Centre), patients diagnosed with ILC had an insignificant better survival trend than patients with IDC (91.02 vs 84.32%). These differences have been explained by more frequent grade 1 lesions in patients with ILC than in those with IDC (Ugnat et al. 2004).
Differences in metastatic behaviour between ILC and IDC
Some authors did not report any difference in metastatic pattern between ILC and IDC (Du Toit et al. 1991), while others have reported significant differences in the rate of visceral recurrences (Borst & Ingold 1993, Sastre-Garau et al. 1996, Mersin et al. 2003).
In the study by Arpino et al. ILC is more likely to metastasize to the peritoneum, ovaries (2.2 vs 0.7%, P = 0.0003) and gastrointestinal tract (4.5 vs 1.1%, P = 0.009). Conversely, the distant nodes, lungs/pleura and central nervous system are more frequently involved in IDC (Arpino et al. 2004). Korhonen et al.(2004) have confirmed this tendency of ILC to metastasize to the genital organs and gastrointestinal tract (16% for ILC versus 1% for IDC, P = 0.002), whereas no difference was observed in liver, bone or pulmonary-pleural recurrences. In these two studies the authors reported only few metastases to the endocrine organs, whereas an autopsy study found endocrine metastases in 91% patients with metastastic ILC and in 58% patients with IDC (Bumpers et al. 1993). This is probably due to the fact that most endocrine metastases are silent during lifetime and will not be diagnosed (Korhonen et al. 2004).
The median interval between diagnosis and presentation of metastases from breast carcinoma to the gastrointestinal tract varies in most series from 5 to 6 years, although 10 years or more have rarely been reported (Bamias et al. 2001). The clinical presentation of metastatic disease to the gastrointestinal tract is not definite. Symptoms may be non-specific or striking similar to that of primary gastrointestinal malignancies such as obstruction, haemorrhage or perforation (Lagendijk et al. 1999). For this reason, endoscopy should be performed in all cases of suspected colorectal metastatic lesions in order to accurately detect their site and because endoscopic appearance of metastatic lesions may differ from that of a primary carcinoma. In a review, the metastases to the gastrointestinal tract have been found to appear as diffuse thickening and rigidity of the colonic wall mimicking plastic linitis, Chrohn’s-like appearance and ulcerated or nodular areas rather than solitary, discrete masses (Bamias et al. 2001). Histologically, metastases from lobular tumours often do not form glands or tubular structures but infiltrate as small nests and strands of tumour cells, which are usually of the ‘signet-ring’ type. Histopathological diagnosis can be difficult, particularly, for pathologists who are unaware of the patient’s history and the ‘signet-ring’ morphology of lobular carcinoma may be confused with other primary tumours such as gastric carcinoma. Nonetheless, metastatic ILCs are usually positive for gross cystic disease fluid protein-15, ER and PgR, in contrast with most colorectal or gastric carcinomas, which are negative (Lagendijk et al. 1999, Bamias et al. 2001). The reported differences in metastatic pattern between ILC and IDC could be due to a cell size or shape with physical properties that favour certain areas with microanatomy that is more conducive to stopping or trapping these types of cells. Alternatively, the microenvironment of the ovary or peritoneum may provide growth and survival factors that favour ILC cells over IDC cells (Arpino et al. 2004). Additional molecular or biological differences might account for this peculiar pattern of metastasis. The complete loss of E-cadherin expression has been observed in ILC, in contrast with IDC, in which E-cadherin expression is usually maintained. The loss of E-cadherin expression may result in dehiscence of tumour cells, which would allow easier migration of individual tumour cells into the vasculature. In contrast, persistence of E-cadherin in cells that invade the vasculature could lead to the development of intravascular nests of tumour cells or intravascular emboli. It has been proposed that the former mechanism may be operative in E-cadherin negative IDC and in ILC, whereas the latter may occur in E-cadherin positive IDC (Gupta et al. 2003).
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Conclusions |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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ILCs have a substantially increased propensity for multifocal and multicentric distribution and for bilaterality (Sastre-Garau et al. 1996, Toikkanen et al. 1997, Goldflam et al. 2004). Moreover, because of their distinctive growth pattern and biology, lobular carcinomas often fail to form distinct masses that can be easily diagnosed by clinical breast examination or Mx (Rosen 2001). These features can make early diagnosis challenging and breast conservative therapy more difficult.
ILC is generally believed to have more favourable biological features than IDC, with oestrogen and progesterone positive receptors, low grade and low likelihood of lymphatic-vascular invasion. In addition, ILC is characterized by low proliferative activity, C-ErbB-2 negativity, bcl-2 positivity, p53 and VEGF negativity. The lower stage and grade at diagnosis reported in HRT users, who have developed breast cancer when compared with that in non-users, may depend on the higher rate of ILC among HRT users. The lower stage at diagnosis probably reflects also a higher awareness of HRT users for frequent clinical and mammographic screening. Furthermore, women who use HRT tend to belong to the higher socioeconomic classes and have easier access to health facilities (Pappo et al. 2004). Despite the less aggressive biological features of ILC, several studies have not found significant differences in disease-free and OS when compared with IDC (Winchester et al. 1998, Mersin et al. 2003, Arpino et al. 2004, Korhonen et al. 2004, Molland et al. 2004, Ugnat et al. 2004, Santiago et al. 2005).
The role of PCT in ILC should be reconsidered. Only few patients with ILC achieve a pathologic response to PCT and, therefore, may be treated with conservative surgery (Cocquyt et al. 2003, Mathieu et al. 2004, Cristofanilli et al. 2005).
In the following years microarray analysis technology will become undoubtedly an essential tool to understand the role of different patterns of biological markers expression in lobular and ductal breast cancers and to investigate the mechanisms underlying the effect of exogenous steroids on the growth and proliferation of breast cancer.
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Acknowledgements |
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References |
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TopAbstractIntroductionEpidemiologyHRT and breast carcinomaLobular cancersDiagnosis of invasive lobular...Biological and clinical features...Surgical treatment of invasive...Preoperative chemotherapy (PCT)...Prognosis of patients with...ConclusionsReferences |
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