Spectrum of breast cancer metastasis in BRCA1 mutation carriers: highly increased incidence of brain metastases

Albiges, L.; André, Fabrice; Balleyguier, Corinne; Gomez-Abuin, Gonzalo; Chompret, Agnès; Delaloge, Suzette

doi:10.1093/annonc/mdi351

Cited by 86 publications

(51 citation statements)

References 6 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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“…It is known that tumor expression of two other DNA-repair genes, RRM1 and ERCC1, signify a survival advantage for patients with early-stage NSCLC (ref. 28 ) given only surgical treatment. In our study, phospho-BRCA1 expression was also significantly correlated with longer OS and DFS in stage I and II NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer

Gachechiladze¹,

Überall²,

Kolek³

et al. 2013

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a central role in DNA damage response (DDR. It undergoes phosphorylation by various DDR kinases at different serine residues, of which ser1524 is known to be specifically phosphorylated by ATM in response to genotoxic stress. Methods. We performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113 early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were treated by adjuvant cisplatin-based chemotherapy. Staining results were correlated with overall survival (OS), disease free survival (DFS) and with the occurrence of brain metastases. Results. BRCA1 S1524 nuclear positivity was significantly correlated with longer OS and DFS in stage I and II patients (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV patients (P<0.05). No significant correlation was found with brain metastases. Conclusion.The results show that BRCA1 phosphorylaton, at least in ser1524, differentiates the fate of early and advanced NSCLC as well as response to chemotherapy, but the underlying mechanisms are not completely understood. Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and predictive marker for patients with NSCLC.

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“…38 The trend of basal-like cancers to metastasise to brain, 39,40 which was also shown in patients with BRCA1 mutations, is also noteworthy. 41 Can pathology aid clinical decision making?…”

Section: 2829mentioning

confidence: 99%

Pathology of hereditary breast cancer

Silva

Lakhani

2010

Modern Pathology

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Patients with germline mutations in BRCA1 or BRCA2 genes are predisposed to breast cancer. The BRCA1-associated breast cancers have distinct morphology, being more often medullary-like, triple negative and showing a 'basal' phenotype. On the other hand, BRCA2 and BRCAX cancers are a heterogeneous group without a specific phenotype. When incorporated into risk assessment models, pathology data improves prediction of carrier status. The role of BRCA1 and BRCA2 in DNA repair is being exploited to develop novel therapies, for example, using the poly-ADP-ribose polymerase inhibitors. A number of low-to-moderatepenetrant genes/loci have also been identified, but their role and contribution in breast cancer development is still under investigation. Modern Pathology (2010) 23, S46-S51; doi:10.1038/modpathol.2010.37Keywords: BRCA1; BRCA2; BRCAX; breast; hereditary cancer Breast cancer is the commonest malignancy in women and it is estimated that a million women worldwide will develop breast cancer each year. A number of risk factors have been identified including early menarche, late menopause, nulliparity and a positive family history.1 First-degree relatives have an approximately twofold increase in risk of developing the disease. A number of highly penetrant breast cancer susceptibility genes have been identified and include BRCA1 and BRCA2.2,3 These genes confer a high risk of breast and ovarian carcinoma. Two genes associated with rare cancer syndromes, P53 (Li-Fraumeni syndrome) 4 and PTEN (Cowden syndrome) 5 also confer a very high risk of breast cancer. Although all these genes confer a very high risk, they account for a relatively small proportion of inherited breast cancers. It has become increasingly clear that overall susceptibility to breast cancer is likely to be mediated through variants in many genes, each conferring a small-to-moderate risk of the disease. A number of such genes have been reported in the literature and include CHEK2, ATM, NBS1, RAD51, BRIP1 and PALB2.6-10 It is not known how many more genes that confer a small risk are yet to be identified or how these genes come together or interact with each other or with environmental factors to increase the breast cancer risk. BRCA1, BRCA2 and BRCAXThe first high-penetrance gene, BRCA1, was isolated in the year 1994 2,11 and a year later, BRCA2 was localised and cloned. 3,12 Over the last decade, it has been shown that breast cancer arising in patients harbouring a germline mutation in BRCA1 and BRCA2 genes differs from age-matched sporadic breast cancer cases and from familial breast cancers arising in non-BRCA1/2 patients. These differences are in morphology, immunophenotype and molecular characteristics.3,12-29 These differences tell us something about the biology of familial breast cancer, but could also potentially be used in cancer clinics to predict which patients may harbour BRCA1 germline mutation. Cellular Functions of BRCA1 and BRCA2BRCA1 has several cellular roles. It has been implicated in DNA repair, cell-cycle regulation, transcription...

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Spectrum of breast cancer metastasis in BRCA1 mutation carriers: highly increased incidence of brain metastases

Cited by 86 publications

References 6 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

Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer

Pathology of hereditary breast cancer

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