Surveillance for familial breast cancer: Differences in outcome according to BRCA mutation status

Abstract

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.

Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience

“…[32][33][34][35] Although most studies show a similar prognosis for women with hereditary breast cancers compared with age-matched women with sporadic breast cancers, 34,[36][37][38][39][40] other studies have reported worse survival outcomes. [41][42][43] Despite younger age at presentation, we found that the risk of breast cancer recurrence and death was similar between BRCA carriers and noncarriers in the first 5 years Abbreviations: AT, anthracycline-taxane-containing regimens; BCS, breastconserving surgery; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2; OS, overall survival; pCR, pathologic complete response; PR, progesterone receptor; RFS, recurrence-free survival.…”

Outcomes of breast cancer patients with and without BRCA1/2 mutations

“…New data suggest that more effective preventive interventions than a simple regular surveillance proposed by the present study 1 for women at increased familial risk of breast cancer are needed for improved outcome. In this study, carriers of BRCA1 mutations fared significantly worse, even when their tumors were diagnosed at an apparently early stage.…”

“…4 Among 442 patients with a breast cancer diagnosis, BRCA1 carriers had a worse prognosis than BRCA2 carriers and non-BRCA carriers. 1 Although very small number of BRCA2 carriers (n 5 35) and BRCA1 mutation carriers (n 5 89) is subject to biases and errors, the result is to be expected given that most BRCA1 tumors are histopathologically triple negative tumors (ER/PR/HER2 negative) or basal-like subtype 5 in microarray analysis with a worse survival than patients with BRCA2 tumors with a luminal-like subtype (ER-positive). 6 The opposite and unexpected result with better survival for breast cancer patients with BRCA1 than those with BRCA2 mutation is difficult to be explained.…”

Triple-Negative versus Non–Triple-Negative Breast Cancers in High-Risk Women: Phenotype Features and Survival from the HIBCRIT-1 MRI-Including Screening Study

“…An elevated percentage of TNBCs and reduced survival rates are expected for high-risk women, mainly in view of the high susceptibility of BRCA1 mutation carriers to develop cancers of the aggressive basal-like phenotype, frequently associated with hormone receptor negativity, and lack of HER2 overexpression (13)(14)(15)(16). In this context, a number of studies demonstrated the capability of annual multimodal screening programs including magnetic resonance imaging (MRI) to provide an earlier diagnosis of breast cancer in asymptomatic high-risk women (17)(18)(19)(20)(21)(22)(23)(24)(25), leading to expectations for a possible improvement in the outcome of screened high-risk women who are diagnosed with breast cancer.…”