Disruption of the expected positive correlation between breast tumor size and lymph node status in <i>BRCA1</i>‐related breast carcinoma

Foulkes, William D.; Metcalfe, Kelly; Hanna, Wedad; Lynch, Henry T.; Ghadirian, Parviz; Tung, Nadine; Olopade, O. I.; Weber, Barbara; McLennan, Jane; Olivotto, Ivo A.; Sun, Ping; Chappuis, Pierre O.; Bégin, Louis R.; J, Brunet; Narod, Steven A.

doi:10.1002/cncr.11688

Cited by 105 publications

(67 citation statements)

References 33 publications

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“…Future studies should evaluate the usefulness of this marker for more accurately predicting the probability of carrying a BRCA1 mutation, as has been suggested for CK5/6. Interestingly, previous studies have shown a characteristic pattern of metastatic spread in familial BRCA1 tumors consisting of a low incidence of lymphatic spread to the axillary nodes, but a high incidence of hematogenous spread, mainly to the lung and brain (53,54). This pattern of spread is similar to that observed in the work of Minn et al (8) and in the present series, and suggests that it is related with a basal phenotype.…”

Section: Discussionsupporting

confidence: 91%

Prognostic Significance of Basal-Like Phenotype and Fascin Expression in Node-Negative Invasive Breast Carcinomas

Rodríguez‐Pinilla¹,

Sarrió²,

Honrado

et al. 2006

Clinical Cancer Research

314

219

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Purpose: Basal-like phenotype tumors are frequently found among BRCA1 germ-line mutated breast carcinomas. They are biologically aggressive and have a tendency towards visceral metastasis when untreated. Nevertheless, it has been suggested that they respond to chemotherapy better than other types of tumors. Fascin expression has been associated with lung metastasis in breast cancer. The aim of this study was to determine whether basal-like phenotype and fascin were related in both sporadic and familial tumors and with prognosis in node-negative sporadic breast cancers. Experimental Design: 230 nonfamilial and 28 hereditary node-negative invasive breast carcinomas were immunohistochemically analyzed using tissue microarrays. Tumors that were estrogen receptor/HER2 negative and cytokeratin 5/6 and/or epidermal growth factor receptor positive were considered to have a basal-like phenotype. Results: A basal-like phenotype was found in 11.9% of sporadic cancers. Among patients not receiving adjuvant chemotherapy, a basal-like phenotype was associated with poor prognosis (P = 0.001, log-rank test) whereas no such association was found in patients receiving it. Tumors with a basal-like phenotype showed local recurrence (17.4%) or visceral metastasis (13%) but not bone metastasis (P = 0.001). Fascin expression was observed in 25.1% of sporadic invasive breast carcinomas and was associated with the basal-like phenotype, but not with prognosis or recurrence pattern. Fascin was expressed in 83.3% and 16.7% BRCA1-and BRCA2-associated carcinomas, respectively (P = 0.048). Conclusions: Basal-like tumors had a tendency towards visceral metastasis and their prognosis was dependent on the use of postoperative chemotherapy. Although fascin expression was associated with the basal-like phenotype, it was not associated with their metastatic behavior. Fascin expression is frequent in BRCA1-associated tumors.

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Section: Discussionsupporting

confidence: 91%

Prognostic Significance of Basal-Like Phenotype and Fascin Expression in Node-Negative Invasive Breast Carcinomas

Rodríguez‐Pinilla¹,

Sarrió²,

Honrado

et al. 2006

Clinical Cancer Research

314

219

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“…2). This result confirms and extends our original observations discussed above (53,54), and given that basal breast cancers are associated with a worse prognosis than nonbasal breast cancers (8,9,55), suggests that the mechanism of metastatic spread may be different for this subtype of breast cancer. This view is supported by the multivariable proportional hazards model, including terms for interactions among P-cadherin, tumor size, and lymph node status ( Table 3).…”

Section: Discussionsupporting

confidence: 91%

“…We previously showed that the expected relationship between increasing tumor size and increasing number of axillary nodes involved by metastatic tumor does not hold equally for BRCA1-related and other types of breast cancer (53). We later showed that this might be a general property of basal breast cancers (11), and this conjecture is supported by the data shown here.…”

Section: Discussionsupporting

confidence: 72%

Placental Cadherin and the Basal Epithelial Phenotype of BRCA1-Related Breast Cancer

Arnes

Brunet

Stefansson

et al. 2005

Clinical Cancer Research

Self Cite

148

106

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Purpose: BRCA1-related breast cancer frequently has a basal epithelial phenotype, and P-cadherin is a basal marker. We undertook a detailed evaluation of the relationship among P-cadherin, prognostic markers in breast cancer, and outcome. Experimental Design: This study was restricted to 292 cases of first primary invasive breast cancer diagnosed in Ashkenazi Jewish women between 1980 and 1995. All available blocks were stained for P-cadherin, and 261 were included in the final statistical analyses, including 27 germ line BRCA1 mutation carriers and 8 BRCA2 mutation carriers. Descriptive analyses were done followed by survival analyses and a Poisson regression analysis. Results: P-cadherin was present in 80 of the 261breast cancers (31%) and was more frequently present in tumors that have a basal epithelial phenotype [i.e., high-grade, estrogen receptor^and KIP1 (p27 Kip1)^negative tumors, with expression of cytokeratin 5/6, cyclin E,TP53, and presence of BRCA1 mutations and vascular nests (all P < 0.001)]. In a univariate survival model, expression of P-cadherin was associated with a relative risk (RR) of death from breast cancer at a 10-year follow-up of 2.9 (95% confidence interval, 1.8-4.7; P < 0.0001) and was a predictor of poor univariate survival in both lymph node^negative and^positive breast cancers. In a multivariate analysis, the effect of P-cadherin levels was not independent of other basal-related markers. Multivariable interaction modeling showed that P-cadherin positivity was highly predictive of a poor prognosis in small, node-negative breast cancers (RR, 7.1; P = 0.006). Conclusions: P-cadherin is a marker for basal-like breast cancers and is strongly associated with the presence of a BRCA1 mutation. It is an adverse prognostic factor, particularly in small, node-negative breast cancers.

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“…It has been reported than more than 70% of BRCA1 tumors are grade 3, compared with 35% in sporadic cancer (Lakhani et al, 1997(Lakhani et al, , 2000Armes et al, 1998;Lynch et al, 1998;Quenneville et al, 2002;Goffin et al, 2003;Palacios et al, 2003;Eerola et al, 2005a). Other interesting aspects described in BRCA1 tumors are the scarce or absent ductal in situ component accompanying the invasive ductal component (Lakhani et al, 1997), and the disruption of the expected positive correlation between breast tumor size and lymph node status (Foulkes et al, 2003a). These two aspects of BRCA1 tumors have been associated with the fast growth of these tumors, often presented as interval cancers (Brekelmans et al, 2001).…”

Section: Morphology Of Brca1-and Brca2-associated Tumorsmentioning

confidence: 99%

Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

et al. 2006

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Tumors arising in BRCA1 and BRCA2 mutation carriers appear to have specific pathological and gene expression profiles, which show a high level of concordance. BRCA1 tumors are high-grade, negative for hormone receptors, have a high proliferation rate, and are positive for some cell cycle promoter genes. BRCA2 tumors present a phenotype opposite to BRCA1 tumors but very similar to sporadic tumors, except that BRCA2 overexpress some DNA repair markers such as CHEK2, show high cytoplasmic expression of RAD51, and are negative for HER-2 amplification and expression. Some of these characteristics have also been found in cDNA expression studies, although more analysis are necessary in order to obtain new markers that can be associated with a germ line mutation in BRCA1 or BRCA2. In this way, some studies in normal tissues of BRCA1/2 carriers suggest that differences exist in the level of expression of some genes when compared with noncarriers. Finally, IHC studies in tumors carrying a mutation in CHEK2 are rare and show contradictory results, probably due to the low number of these cases. However, they represent an example showing how different mutations of the same gene may be associated with specific histological subtypes of cancer.

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Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1‐related breast carcinoma

Cited by 105 publications

References 33 publications

Prognostic Significance of Basal-Like Phenotype and Fascin Expression in Node-Negative Invasive Breast Carcinomas

Prognostic Significance of Basal-Like Phenotype and Fascin Expression in Node-Negative Invasive Breast Carcinomas

Placental Cadherin and the Basal Epithelial Phenotype of BRCA1-Related Breast Cancer

Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

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