Limits...
Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival.

Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, Easton D, Lakhani SR - Breast Cancer Res. (2007)

Bottom Line: In patients without metastatic disease, disease-free survival in CK14-positive cases was significantly better than in CK14-negative cases (HR 0.65, p = 0.005).In patients with metastatic disease, however, CK14 positivity was associated with a poorer prognosis (HR 1.84, p = 0.001).These results demonstrate that basal-like tumours differ in their biological behaviour from other tumours, with a distinct pattern of metastatic spread.

View Article: PubMed Central - HTML - PubMed

Affiliation: Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK. laura.work@gmail.com

ABSTRACT

Introduction: Cytokeratin (CK) 14, one of several markers expressed in normal myoepithelial/basal cells, is also expressed in a proportion of breast carcinomas. Previous studies have suggested that expression of such 'basal' markers predicts different biological behaviour, with more frequent lung and brain metastases and poorer prognosis than other carcinomas.

Methods: We performed CK14 immunohistochemistry on 443 grade III invasive ductal carcinomas with extended clinical follow-up (mean 116 months), and we correlated CK14 immunopositivity (basal-like phenotype) with clinicopathological criteria.

Results: Eighty-eight of 443 (20%) tumours showed CK14 expression. CK14-positive tumours were more likely to be oestrogen receptor-negative (p < 0.0001) and axillary node-negative (p = 0.001) than were CK14-negative cases. CK14-positive cases developed less bone and liver metastases (hazard ratio [HR] 0.49, p = 0.01, and HR 0.53, p = 0.035, respectively) but more frequent brain metastases (HR 1.92, p = 0.051). In patients without metastatic disease, disease-free survival in CK14-positive cases was significantly better than in CK14-negative cases (HR 0.65, p = 0.005). In patients with metastatic disease, however, CK14 positivity was associated with a poorer prognosis (HR 1.84, p = 0.001). The overall survival in CK14-positive and -negative patients was similar at 5 years (60% and 59%, respectively), but the long-term survival was better in CK14-positive patients (HR 0.69, p = 0.02).

Conclusion: These results demonstrate that basal-like tumours differ in their biological behaviour from other tumours, with a distinct pattern of metastatic spread. Compared to other grade III tumours, basal-like tumours appear to have a relatively good long-term survival but survival after metastases is poor.

Show MeSH

Related in: MedlinePlus

Histological appearance of basal tumours and CK14 expression patterns. (a) Typical histological appearance of a basal breast carcinoma (haematoxylin and eosin). (b) CK14 expression: a basal tumour with basal keratin expression in almost every tumour cell (diffuse staining pattern). (c) Another basal tumour with only a minority of tumour cells showing expression (focal staining pattern).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1851397&req=5

Figure 1: Histological appearance of basal tumours and CK14 expression patterns. (a) Typical histological appearance of a basal breast carcinoma (haematoxylin and eosin). (b) CK14 expression: a basal tumour with basal keratin expression in almost every tumour cell (diffuse staining pattern). (c) Another basal tumour with only a minority of tumour cells showing expression (focal staining pattern).

Mentions: Morphologically, these tumours are predominantly of high grade [9,19,23-26,29,35] and more frequently show medullary-like features [30,31] and metaplastic elements [19,20,32,33,36-39] (Figure 1a). Immunohistochemically, they are predominantly oestrogen receptor (ER)-, progesterone receptor (PR)-, and C-erb B2 receptor (HER2)-negative [19,22,24,25,32]. These characteristics also predominate among tumours arising in patients with germline BRCA1 (breast cancer 1, early onset) mutations [40,41]. Recent studies have indicated that positive staining for 'basal' markers in patients with familial breast and/or ovarian tumours is strongly predictive of carrying a BRCA1 mutation [27,34,41]; however, there are several lines of evidence to suggest that sporadic basal-like ductal carcinomas do not harbour BRCA1 somatic mutations [42].


Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival.

Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, Easton D, Lakhani SR - Breast Cancer Res. (2007)

Histological appearance of basal tumours and CK14 expression patterns. (a) Typical histological appearance of a basal breast carcinoma (haematoxylin and eosin). (b) CK14 expression: a basal tumour with basal keratin expression in almost every tumour cell (diffuse staining pattern). (c) Another basal tumour with only a minority of tumour cells showing expression (focal staining pattern).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851397&req=5

Figure 1: Histological appearance of basal tumours and CK14 expression patterns. (a) Typical histological appearance of a basal breast carcinoma (haematoxylin and eosin). (b) CK14 expression: a basal tumour with basal keratin expression in almost every tumour cell (diffuse staining pattern). (c) Another basal tumour with only a minority of tumour cells showing expression (focal staining pattern).
Mentions: Morphologically, these tumours are predominantly of high grade [9,19,23-26,29,35] and more frequently show medullary-like features [30,31] and metaplastic elements [19,20,32,33,36-39] (Figure 1a). Immunohistochemically, they are predominantly oestrogen receptor (ER)-, progesterone receptor (PR)-, and C-erb B2 receptor (HER2)-negative [19,22,24,25,32]. These characteristics also predominate among tumours arising in patients with germline BRCA1 (breast cancer 1, early onset) mutations [40,41]. Recent studies have indicated that positive staining for 'basal' markers in patients with familial breast and/or ovarian tumours is strongly predictive of carrying a BRCA1 mutation [27,34,41]; however, there are several lines of evidence to suggest that sporadic basal-like ductal carcinomas do not harbour BRCA1 somatic mutations [42].

Bottom Line: In patients without metastatic disease, disease-free survival in CK14-positive cases was significantly better than in CK14-negative cases (HR 0.65, p = 0.005).In patients with metastatic disease, however, CK14 positivity was associated with a poorer prognosis (HR 1.84, p = 0.001).These results demonstrate that basal-like tumours differ in their biological behaviour from other tumours, with a distinct pattern of metastatic spread.

View Article: PubMed Central - HTML - PubMed

Affiliation: Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK. laura.work@gmail.com

ABSTRACT

Introduction: Cytokeratin (CK) 14, one of several markers expressed in normal myoepithelial/basal cells, is also expressed in a proportion of breast carcinomas. Previous studies have suggested that expression of such 'basal' markers predicts different biological behaviour, with more frequent lung and brain metastases and poorer prognosis than other carcinomas.

Methods: We performed CK14 immunohistochemistry on 443 grade III invasive ductal carcinomas with extended clinical follow-up (mean 116 months), and we correlated CK14 immunopositivity (basal-like phenotype) with clinicopathological criteria.

Results: Eighty-eight of 443 (20%) tumours showed CK14 expression. CK14-positive tumours were more likely to be oestrogen receptor-negative (p < 0.0001) and axillary node-negative (p = 0.001) than were CK14-negative cases. CK14-positive cases developed less bone and liver metastases (hazard ratio [HR] 0.49, p = 0.01, and HR 0.53, p = 0.035, respectively) but more frequent brain metastases (HR 1.92, p = 0.051). In patients without metastatic disease, disease-free survival in CK14-positive cases was significantly better than in CK14-negative cases (HR 0.65, p = 0.005). In patients with metastatic disease, however, CK14 positivity was associated with a poorer prognosis (HR 1.84, p = 0.001). The overall survival in CK14-positive and -negative patients was similar at 5 years (60% and 59%, respectively), but the long-term survival was better in CK14-positive patients (HR 0.69, p = 0.02).

Conclusion: These results demonstrate that basal-like tumours differ in their biological behaviour from other tumours, with a distinct pattern of metastatic spread. Compared to other grade III tumours, basal-like tumours appear to have a relatively good long-term survival but survival after metastases is poor.

Show MeSH
Related in: MedlinePlus