BRCA-associated breast cancer in young women.

Robson, Mark E.; Gilewski, Theresa; Haas, Bruce R.; Levin, D; Borgen, Patrick I.; Rajan, Prabha; Hirschaut, Y; Pressman, Peter I.; Rosen, Paul Peter; Lesser, Martin; Norton, Larry; Offit, Kenneth

doi:10.1200/jco.1998.16.5.1642

Cited by 281 publications

(158 citation statements)

References 14 publications

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“…HER2/neu expression was infrequent and did not differ between the BRCA1-related tumours and the controls, which is in line with previous findings (Lynch et al, 1998). In accordance with previous publications concerning E-cadherin expression in BRCA1 carriers (Robson et al, 1998;Armes et al, 1999;Jacquemier et al, 1999), we did not observe different expression levels.…”

Section: Discussionsupporting

confidence: 93%

“…Also, in accordance with other studies (Lakhani et al, 1997;Armes et al, 1998), the BRCA1-related tumours were associated with a lower frequency of in situ carcinoma. The trend towards higher incidence of lymphangio invasion was not found by others (Armes et al, 1998;Robson et al, 1998). Armes et al, reported a significantly lower proportion of tumours showing cyclin D1 over-expression among BRCA1-related tumours (Armes et al, 1999).…”

Section: Discussionmentioning

confidence: 84%

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Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

Bock¹,

Tollenaar²,

Papelard³

et al. 2001

Br J Cancer

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Several studies have investigated the differences in tumour characteristics between breast cancer in BRCA1-carriers and other patients, aiming to obtain insight into features that might be of importance for recognizing patients with BRCA1-related tumours. In many studies, it was observed that BRCA1-associated breast cancers are more frequently histologic grade 3 (Eisinger et al, 1996;Marcus et al, 1996;Johannsson et al, 1997;Karp et al, 1997;Lakhani et al, 1997;Armes et al, 1998;Lynch et al, 1998) and that they express receptors for oestrogen and progesterone less frequently (Johannsson et al, 1997;Karp et al, 1997;Lynch et al, 1998;Loman et al, 1998Verhoog et al, 1998Armes et al, 1999). Both features are usually associated with a poorer prognosis.However, all studies were performed on highly selected groups of patients, which might lead to survival bias and underestimation of the differences under study. The majority of studies examined tumours from families with a high incidence of breast cancer (Eisinger et al, 1996;Marcus et al, 1996;Johannsson et al, 1997;Lakhani et al, 1997;Loman et al, 1998;Lynch et al, 1998;Verhoog et al, 1998), from patients with an early onset breast cancer (Armes et al, 1998(Armes et al, , 1999, or from specific populations with founder mutations (Karp et al, 1997). Moreover, in most studies in which the cases were selected from breast cancer families, the controls were breast cancer patients without a positive family history but no definite proof of a negative BRCA1 mutations status (Eisinger et al, 1996;Verhoog et al, 1998) or an unknown family history (Marcus et al, 1996;Johannsson et al, 1997;Lakhani et al, 1997). This might also give an underestimation of the differences under study.Recently, we completed a BRCA1 mutation screening study on a hospital-based cohort of 642 breast cancer patients not selected for family history or age at diagnosis. BRCA1-germline mutations were identified in 10 patients by using a mutation-scanning assay that would detect approximately 70% of the currently known Dutch mutation spectrum (Papelard et al, 2000). The aim of this analysis is to investigate the clinical and pathological features of these BRCA1 associated carcinomas as compared to other breast cancers in a representative sample. METHODS Patients and SettingPopulation From January 1984 until November 1996 all primary invasive breast cancer patients surgically treated at the Leiden University Medical Centre (LUMC) regardless of age or family history have been asked to provide a blood sample for research purposes. Mutation screening of BRCA1 was performed anonymously using an assay targeted at known founder mutations in the Dutch population. In brief, 15 PCR-amplifiers covered gene regions known to Summary Thus far, studies investigating the differences in tumour characteristics between breast cancer in BRCA1-carriers and other patients, have focused on highly selected groups of patients, potentially limiting the conclusions that can be drawn. Previously, we had identified 10 patients with BR...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 84%

Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

Bock¹,

Tollenaar²,

Papelard³

et al. 2001

Br J Cancer

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“…We did not have the estrogen-receptor status of the breast cancers in this study; however, it is expected that the majority of BRCA1-associated breast cancers will be ER-negative and that the majority of BRCA2-associated breast cancers will be ER-positive. [4][5][6][7][8][9] These and previous data suggest that tamoxifen is effective in preventing ER-negative second primary cancers. The estrogen-receptor status of the first breast cancer does not influence the actuarial risk of contralateral breast cancer in BRCA1 carriers.…”

Section: Discussionmentioning

confidence: 64%

Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update

Gronwald

Tung

Foulkes

et al. 2005

Intl Journal of Cancer

232

123

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Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of 80%, and following the first diagnosis the 10-year risk of contralateral breast cancer is 30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30-0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17-1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR 5 0.83; 95%CI, 0.24-2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR 5 0.44; 95% CI, 0.27-0.65). ' 2005 Wiley-Liss, Inc.Key words: breast cancer; tamoxifen; oophorectomy; BRCA1; BRCA2The lifetime risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation is 80%, 1 and following an initial diagnosis of breast cancer the annual risk of contralateral breast cancer is 3%. 2 Both tamoxifen and oophorectomy have been shown to reduce the risk of contralateral breast cancer in carriers of BRCA1 or BRCA2 mutations. 2,3 In our previous case-control study of 209 bilateral cases and 384 unilateral controls we reported a reduction in contralateral breast cancer risk of 51% associated with tamoxifen use, but the observed protective effect was significant only in BRCA1 carriers. Since this report was published in 2000, we have continued to accrue study subjects to our BRCA carrier registry and we are able to readdress the question of tamoxifen protection with a greater degree of precision and are able to evaluate the magnitude of the protective effect separately for carriers of BRCA1 and BRCA2 mutations. It is also of interest to establish whether or not there is a protective effect of tamoxifen in women who have previously undergone an oophorectomy and to evaluate the protective effect separately for pre and postmenopausal women. Material and methods Study subjectsInformation on patients with hereditary breast cancer was submitted to the study center by investigators at each of 49 contributing centers in 10 countries. These centers were requested to complete data forms for all known cases of female breast cance...

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“…In BRCA1-associated breast cancer, immunohistochemical detection of ErbB2 overexpression is usually found in less than 25% of cases (Johannsson et al, 1997;Robson et al, 1998). In our study, immunohistochemical and Western analysis on primary tumors and cell lines from Brca1 conditional knockout mice demonstrated ErbB2 overexpression.…”

Section: Discussionmentioning

confidence: 74%

Multiple genetic changes are associated with mammary tumorigenesis in Brca1 conditional knockout mice

et al. 2001

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Germline mutations in the tumor suppressor gene BRCA1 predispose women to breast cancer, however somatic mutations in the gene are rarely detected in sporadic cancers. To understand this phenomenon, we examined mouse models carrying conditional disruption of Brca1 in mammary epithelium in either p53 wild type (wt) or heterozygous backgrounds. Although a p53 +/7 mutation signi®cantly accelerated tumorigenesis, both strains developed mammary tumors in a stochastic fashion, suggesting that multiple factors, in addition to p53 mutations, may be involved in Brca1 related tumorigenesis. A unique feature of Brca1 mammary tumors is their highly diverse histopathology accompanied by severe chromosome abnormalities. The tumors also display extensive genetic/molecular alterations, including overexpression of ErbB2, c-Myc, p27 and Cyclin D1 in the majority of tumors, while they were virtually ERa and p16 negative. Translocations involving p53 were also identi®ed which lead to abnormal RNA and protein products. In addition, we generated cell lines from mammary tumors and found that the cells retained many of the genetic changes found in the primary tumors, suggesting that these genes may be players in Brca1-associated tumorigenesis. Despite their distinct morphology, all cultured tumor cells were Tamoxifen resistant but highly sensitive to Doxorubicin or girradiation, suggesting that these methods would be e ective in treatment of this disease. Oncogene (2001) 20, 7514 ± 7523.

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BRCA-associated breast cancer in young women.

Cited by 281 publications

References 14 publications

Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients

Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update

Multiple genetic changes are associated with mammary tumorigenesis in Brca1 conditional knockout mice

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