Accuracy of screening women at familial risk of breast cancer without a known gene mutation:individual patient data meta-analysis

Introduction Women with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program. Methods An individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI. Results There were 2226 women (median age: 41 years, interquartile range 35–47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3–14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P &lt; 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P &lt; 0.01 compared with mammography alone). Conclusion In this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity.</p

The supplemental value of mammographic screening over breast MRI alone in BRCA2 mutation carriers

Purpose BRCA2 mutation carriers are offered annual breast screening with MRI and mammography. The aim of this study was to investigate the supplemental value of mammographic screening over MRI screening alone. Methods In this multicenter study, proven BRCA2 mutation carriers, who developed breast cancer during screening using both digital mammography and state-of-art breast MRI, were identified. Clinical data were reviewed to classify cases in screen-detected and interval cancers. Imaging was reviewed to assess the diagnostic value of mammography and MRI, using the Breast Imaging and Data System (BI-RADS) classification allocated at the time of diagnosis. Results From January 2003 till March 2019, 62 invasive breast cancers and 23 ductal carcinomas in situ were diagnosed in 83 BRCA2 mutation carriers under surveillance. Overall screening sensitivity was 95.2% (81/85). Four interval cancers occurred (4.7% (4/85)). MRI detected 73 of 85 breast cancers (sensitivity 85.8%) and 42 mammography (sensitivity 49.9%) (p < 0.001). Eight mammography-only lesions occurred. In 1 of 17 women younger than 40 years, a 6-mm grade 3 DCIS, retrospectively visible on MRI, was detected with mammography only in a 38-year-old woman. The other 7 mammography-only breast cancers were diagnosed in women aged 50 years and older, increasing sensitivity in this subgroup from 79.5% (35/44) to 95.5% (42/44) (p <= 0.001). Conclusions In BRCA2 mutation carriers younger than 40 years, the benefit of mammographic screening over MRI was very small. In carriers of 50 years and older, mammographic screening contributed significantly. Hence, we propose to postpone mammographic screening in BRCA2 mutation carriers to at least age 40.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Benefits of preoperative MRI in breast cancer surgery studied in a large population-based cancer registry

Background: Although evidence for the benefits of preoperative MRI in breast cancer is lacking, use of MRI is increasing and characterized by large interhospital variation. The aim of the study was to evaluate MRI use and surgical outcomes retrospectively. Methods: Women with invasive breast cancer (pT1-3) or ductal carcinoma in situ (DCIS), diagnosed in 2011-2013, were selected from the Netherlands Cancer Registry and subdivided into the following groups: invasive cancer, high-grade DCIS, non-palpable cancer, age 40 years or less, and invasive lobular cancer. Associations between preoperative MRI use and initial mastectomy, resection margin after breast-conserving surgery (BCS), re-excision after BCS, and final mastectomy were analysed. Results: In total, 5514 women were included in the study; 1637 (34.1 per cent) of 4801 women with invasive cancer and 150 (21.0 per cent) of 713 with DCIS had preoperative MRI. Positive resection margins were found in 18.1 per cent women who had MRI and in 15.1 per cent of those who did not (adjusted odds ratio (OR) 1.20, 95 per cent c.i. 1.00 to 1.45), with no differences in subgroups. Re-excision rates were 9.8 per cent in the MRI group and 7.2 per cent in the no-MRI group (adjusted OR 1.33, 1.04 to 1.70), with no differences in subgroups. In the MRI group, 38.8 per cent of patients ultimately underwent mastectomy, compared with 24.2 per cent in the no-MRI group (adjusted OR 2.13, 1.87 to 2.41). This difference was not found for patients aged 40 years or less, or for those diagnosed with lobular cancer. Conclusion: No subgroup was identified in which preoperative MRI influenced the risk of margin involvement or re-excision rate after BCS. MRI was significantly associated with more extensive surgery, except in patients aged 40 years or less and those with invasive lobular cancer. These results suggest that use of preoperative MRI should be more targeted, and that general, widespread use be discouraged

Cost-effectiveness of Screening with Additional MRI for Women with Familial Risk for Breast Cancer Without a Genetic Predisposition

Surgical oncolog

Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.

Contains fulltext : 58587.pdf (publisher's version ) (Open Access)BACKGROUND: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. METHODS: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups. RESULTS: We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. CONCLUSIONS: MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer

The supplemental value of mammographic screening over breast MRI alone in BRCA2 mutation carriers

Contains fulltext : 220728.pdf (Publisher’s version ) (Open Access)PURPOSE: BRCA2 mutation carriers are offered annual breast screening with MRI and mammography. The aim of this study was to investigate the supplemental value of mammographic screening over MRI screening alone. METHODS: In this multicenter study, proven BRCA2 mutation carriers, who developed breast cancer during screening using both digital mammography and state-of-art breast MRI, were identified. Clinical data were reviewed to classify cases in screen-detected and interval cancers. Imaging was reviewed to assess the diagnostic value of mammography and MRI, using the Breast Imaging and Data System (BI-RADS) classification allocated at the time of diagnosis. RESULTS: From January 2003 till March 2019, 62 invasive breast cancers and 23 ductal carcinomas in situ were diagnosed in 83 BRCA2 mutation carriers under surveillance. Overall screening sensitivity was 95.2% (81/85). Four interval cancers occurred (4.7% (4/85)). MRI detected 73 of 85 breast cancers (sensitivity 85.8%) and 42 mammography (sensitivity 49.9%) (p < 0.001). Eight mammography-only lesions occurred. In 1 of 17 women younger than 40 years, a 6-mm grade 3 DCIS, retrospectively visible on MRI, was detected with mammography only in a 38-year-old woman. The other 7 mammography-only breast cancers were diagnosed in women aged 50 years and older, increasing sensitivity in this subgroup from 79.5% (35/44) to 95.5% (42/44) (p </= 0.001). CONCLUSIONS: In BRCA2 mutation carriers younger than 40 years, the benefit of mammographic screening over MRI was very small. In carriers of 50 years and older, mammographic screening contributed significantly. Hence, we propose to postpone mammographic screening in BRCA2 mutation carriers to at least age 40

BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study.

Contains fulltext : 88479.pdf (publisher's version ) (Open Access

Hereditary breast cancer growth rates and its impact on screening policy

Contains fulltext : 47763.pdf (publisher's version ) (Closed access)Imaging is often performed yearly for the surveillance of BRCA1/2 mutation carriers and women at high familial breast cancer risk. Growth of cancers in carriers may be faster as these tumours are predominantly high grade. Quantitative data on tumour growth rates in these 2 groups are lacking. Here, we have examined 80 high-risk women under surveillance for tumour size at diagnosis and preceding examinations at mammography and/or MRI. Tumour volume doubling time (DT) was assessed in 30 cancers in BRCA1/2 mutation carriers and 25 non-carriers. Impact of age and menopausal status were also evaluated. Mean DT of all invasive cancers was shorter in carriers (45 days CI: 26-73) than non-carriers (84 days CI: 58-131) (P = 0.048). Mean age at diagnosis was lower in carriers (40 years) than non-carriers (45 years) (P = 0.007). At multivariable analysis only age (P = 0.03), not risk-group (P = 0.26) nor menopause (P = 0.58) correlated significantly with DT. The mean growth rate slowed down to half in each successive 10 years-older group. In conclusion, age at detection indicated the growth rates of hereditary and familial breast cancers. It is recommended that the screening frequency should be adjusted according to a woman's age and a high-sensitive biannual test may be appropriate before the age of 40 years