Efficacy of Early Diagnosis and Treatment in Women with a Family History of Breast Cancer

Abstract

BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality.METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan—Meier survival plots.RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first (“prevalence”) round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+.CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of “breast awareness” as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families.

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

“…Between 70 and 80% of cancers were diagnosed in the course of screening examinations, the remainder being interval tumors. 10 There was no significant difference in sensitivity of screening between the 3 patient groups. Tumors were staged as carcinoma in situ (CIS), invasive cancer without nodal spread (CaN0) or cancer with nodal involvement (CaN1).…”

“…For details of inclusion criteria, surveillance protocols and follow-up programmes see previous reports. 9,10 In brief, risk estimation was based on family history but generally without molecular genetic testing prior to inclusion (mutation-testing was usually completed after diagnosis of cancer). Documented and verified family histories predicted lifetime breast cancer risks of 20% or more, indicating that most women had 2 or more affected close relatives.…”

Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy

“…Our population included all patients contracting breast cancer within the observation period, irrespective of diagnostic methods. Most were demonstrated on planned examinations, but some were interval cancers (see previous report for detailed discussion 5 ). Tumours were staged as carcinoma in situ (CIS, ductal or lobular), infiltrating cancer without nodal spread (CaN0) or cancer with spread (CaNϩ).…”

“…For details of the inclusion criteria and follow-up programmes, see previous reports. 4,5 In brief, risk estimations were based on family history but without genetic testing prior to inclusion. Documented family history verified lifetime risk for breast cancer of 20% or more, implying that most women had a number of affected relatives.…”

Breast cancer risk in women who fulfill high-risk criteria: at what age should surveillance start?

“…Thus, women with a strong family history of breast or ovarian cancer are at high risk of breast cancer in spite of a negative genetic test for mutations in BRCA1/2 [2]. Women at high risk of breast cancer might benefit from increased surveillance and risk reducing interventions [9,10]. However, the recommendations for the starting age of screening in high-risk women are mainly based on expert opinion [3].…”