Tumor characteristics and prognosis in familial breast cancer (original) (raw)
Related papers
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2015
Women with inherited pathogenic mutations in the BRCA1 or BRCA2 genes have up to an 85% risk of developing breast cancer in their lifetime. However, only about 20% of familial breast cancer is attributed to mutations in BRCA1 and BRCA2, while a further 5-10% are attributed to mutations in other rare susceptibility genes such as TP53, STK11, PTEN, ATM and CHEK2. Despite extensive efforts to explain the missing heritability of this disease, the majority of familial clustering in breast cancer remains largely unexplained. We aim to analyze the pathology of familial cases of which no pathogenic mutation is yet identified. We compared the pathological phenotype of BRCA1/BRCA2 negative familial breast cancer (BRCAx) to BRCA1-positive, BRCA2-positive and sporadic cases without a family history. Age-adjusted analysis is summarized in odd's ratios and confidence intervals for tumor type, grade, lymph node, ER and HER2 status. We found non-familial cases to be more likely to be ER positiv...
Familial breast cancer: characteristics and outcome of BRCA 1-2 positive and negative cases
BMC cancer, 2005
The clinical and pathological characteristics and the clinical course of patients with breast cancer and BRCA 1-2 mutation are poorly known. From 1997, patients with breast cancer and a family history of breast or ovarian cancer were offered BRCA testing. The clinical and pathological features of patients with known BRCA status were retrospectively assessed and comparisons were made between cancers arising in BRCA positive and BRCA wild type (WT) patients respectively. Type of treatment, pattern of relapse, event (local relapse, contralateral breast cancer, metastases) free and overall survival were also compared in the two groups. Out of the 210 patients tested, 125 had been treated and followed-up at our Institution and were evaluated in this study. BRCA positive patients tended to be more often premenopausal (79% vs 65%) and to have positive lymphnodes (63% vs 49%), poorly differentiated tumours (76% vs 40%--p = 0.002 at univariate analysis, not significant at multivariate analys...
Familial versus Sporadic Breast Cancer: Different Treatments for Similar Tumors?
Advances in Breast Cancer Research, 2015
Objective: It is unclear if and to what extent family history of breast/ovarian cancer or BRCA1/2mutation carriership influences breast cancer treatment strategy. We investigated whether treatment differed between patients from BRCA1/2 families and those unselected for family history. Methods: We included 478 BRCA1/2-related patients referred for genetic testing before or after diagnosis. Two references were used: 13,498 population-based and 6896 hospital-based patients. Surgical treatment and adjuvant chemotherapy use was analyzed using logistic regression models, stratified by tumor size, nodal status, age at and period of diagnosis, and estrogen receptor status (ER). Results: BRCA1/2 cases aged 35-52 years at diagnosis and/or with tumors < 2 cm were more likely to have undergone a modified radical mastectomy (Odd Ratios (OR) ranging from 2.8 to 5.1) compared to the references. This effect was most pronounced in patients treated after 1995 (OR 5.7 to 10.3). Compared to the reference groups, chemotherapy was more often administered to BRCA1 and ER-negative BRCA1/2-cases irrespective of age and nodal status (OR 1.9 E. G. Engelhardt et al. 88 to 24.3). Conclusion: After 1995 treatment of BRCA1/2-associated patients consisted notably of more mastectomies and adjuvant chemotherapy than their population-based counterparts with the same tumor characteristics. There is a need to be aware of such differences in daily practice and interpretation of survival studies on BRCA1/2 mutation carriers.
Etiology of familial breast cancer with undetected BRCA1 and BRCA2 mutations: clinical implications
Cellular Oncology, 2014
Background Familial breast cancer accounts for 20-30 % of all breast cancer cases. Mutations in the BRCA1 and BRCA2 genes account for the majority of high risk families with both early onset breast cancer and ovarian cancer. Most of the families with less than six breast cancer cases and no ovarian cancer do not carry BRCA1 or BRCA2 mutations that can be detected using routine sequencing protocols. Here, we aimed to review the etiology of familial breast cancer in cases without BRCA1 and BRCA2 mutations. Results After excluding BRCA1 and BRCA2 mutations, factors proposed to contribute to familial breast cancer include: chance clustering of apparently sporadic cases, shared lifestyle, monogenic inheritance, i.e., dominant gene mutations associated with a high risk (TP53, PTEN, STK11), dominant gene mutations associated with a relatively low risk (ATM, BRIP1, RLB2), recessive gene mutations associated with horizontal inheritance patterns (sister-sister), and polygenic inheritance where susceptibility to familial breast cancer is thought to be conferred by a large number of low risk alleles. Conclusions Current evidence suggests that in the majority of cases with BRCA1 and BRCA2 negative familial breast cancer the etiology is due to interactions of intermediate or low risk alleles with environmental and lifestyle factors. Thus, a careful selection of patients submitted to genetic testing is needed. Clearly, further research is required to fully elucidate the etiology of non-BRCA familial breast cancer.
Cancers, 2019
Breast cancer (BC) prognosis in BRCA1 and BRCA2 mutation carriers has been reported contradictorily, and the significance of variables influencing prognosis in sporadic BC is not established in BC patients with hereditary BRCA1/BRCA2 mutations. In this retrospective cohort study, we analyzed the effect of clinicopathological characteristics on BC prognosis (disease-free survival [DFS] and disease-specific survival [DSS]) in hereditary BRCA1/BRCA2 mutation carriers. We enrolled 234 BRCA1/BRCA2 mutation carriers and 899 non-carriers, of whom 191 carriers and 680 non-carriers, with complete data, were available for survival analyses. We found that patients
European Journal of Breast Health, 2021
Objective: This study aimed to determine the differences in clinicopathological features of Turkish patients with high-risk breast cancer based on the mutation status of two breast cancer susceptibility genes (BRCA1/2). Materials and Methods: This study enrolled patients with invasive breast cancer who have been evaluated for BRCA1/2 mutations due to the presence of high-risk factors admitted to two tertiary referral centers in Turkey. Clinical and histopathological features were analyzed in BRCA1 mutation carriers, BRCA2 mutation carriers, and non-carriers. Results: A total of 302 patients with a mean age of 44.2±9.9 (22-82) years were included. BRCA1/2 mutation was found in 75 (24%) patients, of whom 41 (13.6%) were BRCA1 mutation carriers and 37 (12.3%) were BRCA2 mutation carriers. Moreover, 104 (34.4%) and 4 (1.3%) patients had family history of breast and ovarian carcinoma, respectively. The rates of triple negativity (56.1%), histologic grade 3 (65.9%), and lymphovascular invasion (78%) were significantly higher in BRCA1 mutation carriers than in non-carriers and BRCA2 mutation carriers. Furthermore, 87% of triple-negative BRCA1 mutation carriers had histologic grade 3 tumors compared with 38.9% in non-triple-negative BRCA1 mutation carriers, and the difference was significant. Conclusion: Findings of this study showed that BRCA1-related breast cancers represent a distinct group with unique pathological features, which are usually associated with a poor prognosis.
International Journal of Cancer, 2002
Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaN0) and 26% had cancer with spread (CaN؉). Five-year survival was 100% for CIS, 94% for CaN0 and 72% for CaN؉ (p ؍ 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p ؍ 0.04). For CaN0 patients, mutation carriers had 75% 5-year disease-free survival vs. 96% for noncarriers (p ؍ 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but 1 relapse occurred in the 15 who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p ؍ 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.
Surveillance for familial breast cancer: Differences in outcome according toBRCA mutation status
International Journal of Cancer, 2007
Women with a family history of breast cancer are commonly offered regular clinical or mammographic surveillance from age 30. Data on the efficacy of such programmes are limited. Clinical, pathological and outcome data were recorded on all breast and ovarian cancers diagnosed within familial breast cancer surveillance programmes at collaborating centers in Norway and the UK up to the end of 2005. These have been analyzed according to the mutation status of the affected women (BRCA11ve, BRCA21ve or mutation-negative). Breast cancer was diagnosed in 442 patients subsequently followed for a total of 2095 years. Eightynine (20%) had BRCA1 mutations, 35 (8%) BRCA2 mutations and in 318 (72%) no mutation could be detected (''mut neg''). Fiveyear survival in BRCA1 was 73% compared to 96% in BRCA2 and 92% in mut neg (p 5 0.000). Among BRCA1 mutation-carriers, 5-year survival was 67% for cases diagnosed as carcinoma in situ, 84% for node-negative invasive cancers and 58% for those with nodal involvement (p > 0.05). For BRCA2 mutation-carriers the corresponding figures were 100, 100 and 90% (p > 0.05), while for mut neg women they were 100, 97 and 71% (p 5 0.03). Regular surveillance in women at increased familial risk of breast cancer is associated with a good outcome if they carry BRCA2 mutations or no detectable mutation. Carriers of BRCA1 mutations fare significantly worse, even when their tumors are diagnosed at an apparently early stage. The differences in outcome associated with different genetic causes of disease were associated with demonstrated differences in tumor biology. The findings demonstrate the outcome for genetically different breast cancers detected within a programme for early diagnosis and treatment, which is relevant to genetic counseling when women at risk have to chose between the options for preventing death from inherited breast cancer. ' 2007 Wiley-Liss, Inc.