A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment

Robson, Mark E.; Chappuis, Pierre O.; Satagopan, Jaya M.; Wong, Nora; Boyd, Jeff; Goffin, John R.; Hudis, Clifford A.; Roberge, David; Norton, Larry; Bégin, Louis R.; Offit, Kenneth; Foulkes, William D.

doi:10.1186/bcr658

Cited by 263 publications

(219 citation statements)

References 41 publications

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“…This observation is substantiated by two earlier studies among Ashkenazi Jewish breast cancer patients. In these studies, BRCA1 status was a strong predictor of breast cancer survival only among women who did not receive chemotherapy, while among women who received chemotherapy it was not (Goffin et al, 2003;Robson et al, 2004).…”

Section: Discussionmentioning

confidence: 96%

“…The risk of local recurrence does not appear to be higher among patients with a strong family history than among low familial risk patients, rendering high familial risk patients equally eligible for breast-conserving surgery (Eccles et al, 2001;Vlastos et al, 2002;Robson et al, 2004). However, their risk for contralateral disease is highly increased (Robson et al, 2004).…”

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confidence: 99%

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Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study

et al. 2005

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This population-based study evaluates the impact of a strong family history of breast cancer on management and survival of women with early-onset disease. We identified all breast cancer patients p50 years, recorded between 1990 and 2001 at the Geneva familial breast cancer registry. We compared patients at high familial risk and low familial risk in terms of tumour characteristics, method of detection, treatment, survival and breast cancer mortality risk. Compared to patients at low familial risk (n ¼ 575), those at high familial risk (n ¼ 58) received significantly more often systemic therapy, especially for node-negative or receptor-positive disease. Five-year disease-specific survival rates of patients at high vs low familial risk were 86 and 90%, respectively. After adjustment, there was no difference in breast cancer mortality in general. A strong family history nonsignificantly increased breast cancer mortality in patients p40 years (adjusted hazard ratio (HR) 4.0, 95% CI 0.8 -19.7) and in patients treated without chemotherapy (adjusted HR 2.7, 95% CI 0.6 -12.5). A strong family history of breast cancer is associated with an increased use of systemic therapy in early-onset patients. Although a strong family history does not seem to affect survival in general, it may impair survival of very young patients and patients treated without adjuvant chemotherapy. Owing to the limited number of patients in this study, these results should be used only to generate hypotheses.

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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study

et al. 2005

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“…25,34,35,[37][38][39][40][41] Between 73 and 90% of BRCA1 carcinomas were estrogen receptor-negative in different series. 34,35,38 For example, Lakhani et al 25 reported that 90% of BRCA1-related breast cancers were estrogen receptor-negative compared with 35% in controls.…”

Section: Familial Breast Cancer Characteristicsmentioning

confidence: 99%

“…Thus, estrogen receptor expression has been reported in around 65% of BRCA2 tumors. 25,38,39 Between 40 and 60% of BRCA2 carcinomas express progesterone receptor 25,38,39 ( Table 2).…”

Section: Familial Breast Cancer Characteristicsmentioning

confidence: 99%

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

2005

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Cancer arising in carriers of mutations in the BRCA1 and BRCA2 genes differs from sporadic breast cancer of age-matched controls and from non-BRCA1/2 familial breast carcinomas in its morphological, immunophenotypic and molecular characteristics. Most BRCA1 carcinomas have the basal cell phenotype, a subtype of highgrade, highly proliferating, estrogen receptor-and HER2-negative breast carcinomas, characterized by the expression of basal or myoepithelial markers such as basal keratins, P-cadherin, epidermal growth factor receptor, etc. This phenotype is rarely found in BRCA2 carcinomas, which are of higher grade than sporadic age-matched controls, but tend to be estrogen receptor-and progesterone receptor-positive. The expression of the cell-cycle proteins cyclins A, B1 and E and SKP2 is associated with a BRCA1 phenotype, whereas cyclin D1 and p27 expression is associated with BRCA2 carcinomas. Recent studies have shown that hereditary carcinomas that are not attributable to BRCA1/2 mutations have phenotypic similarities to BRCA2 tumors, but tend to be of lower grade and proliferation index. Somatic mutations in the BRCA genes are rarely found in hereditary tumors; by contrast, BRCA1 and BRCA2 loss of heterozygosity (LOH) is found in almost all BRCA1 and BRCA2 carcinomas, respectively. Furthermore, all types of hereditary breast carcinomas have a low frequency of HER2 expression. Finally, comparative genomic hybridization studies have revealed differences in chromosomal gains and losses between genotypes. The pathological and molecular features of hereditary breast cancer can drive specific treatments and influence the process of mutation screening. In addition, detecting molecular changes such as BRCA1/2 LOH in nonatypical cells obtained by random fine-needle aspiration, ductal lavage or nipple aspirate fluid may help to earlier identify carrier women who are at an even higher risk of developing breast carcinoma. Keywords: hereditary breast cancer; BRCA1; BRCA2; molecular pathology; histopathology; immunohistochemistry It is currently estimated that 5-10% of all breast cancers are hereditary and attributable to mutations in high-penetrance susceptibility genes, but only two of these have been identified: BRCA1 (OMIM 113705) 1 and BRCA2 (OMIM 600185). 2 BRCA1 mutations are associated with families with breast and ovarian cancer, while families with male breast tumors are associated with mutations in the BRCA2 gene.While early estimates suggested that BRCA1 and BRCA2 mutations were responsible for 75% of multiple-case breast cancer families and for the majority of families with multiple breast and ovarian cancers, 3,4 recent data have shown that these percentages may have been overestimated. In fact, the percentage of high-risk families associated with mutations in these genes seems to be around 25% in all series investigated, including the Spanish population. 5 Mutations are found in a high percentage (about 45%) of families with breast and ovarian tumors, while the mutation rate in families with only breast can...

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“…On the other hand, BRCA2-associated breast carcinomas are rarely basal-like phenotype, also are of higher grade (usually grade 2/3) than sporadic age-matched controls [21], and tend to be ER and PR positive [23].…”

Section: Histological Characterization Of Basal-like Breast Cancersmentioning

confidence: 99%

Histologic diagnosis in young women with breast cancer

Andreu

2010

Breast Cancer Res Treat

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A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment

Abstract: Background: The prognostic significance of germline mutations in BRCA1 and BRCA2 in women with breast cancer remains unclear. A combined analysis was performed to address this uncertainty.

Cited by 263 publications

References 41 publications

Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study

Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

Histologic diagnosis in young women with breast cancer

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