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Diagnosis and Radiologic S Surveillance off BRCA C C Carriers H.M. Zonderland, MD, PhD Radiologist Academic Medical Center Amsterdam, the Netherlands


Purpose p • Recommendations for BRCAmutation carriers: – Surveillance - Multidisciplinary care - Imaging modalities

– Basis B i ffor th the recommendations - Evidence based guidelines of the Netherlands

• Also 1st-degree relatives


I. Surveillance in a Specialized p Institution • Fear and stress • Overestimation of risk • Family affair


II. We Do Not Recommend Regular Breast S lf Examination Self E i ti (BSE) • Regular BSE in women with hereditary breast cancer: – – – –

10% did not perform BSE 13% performed BSE more than once a week 57% performed BSE once a month 20% performed BSE once per 3/6/12 months

van Dooren S, et al. Community Genet. 2003;6(4):235-241.


II. We Do Not Recommend Regular Breast S lf Examination Self E i ti (BSE) • Regular BSE in women with hereditary breast cancer: – – – –

10% did not perform BSE 13% performed BSE more than once a week 57% performed BSE once a month 20% performed BSE once per 3/6/12 months

• Breast awareness: – Symptoms increase the sensitivity of imaging

van Dooren S, et al. Community Genet. 2003;6(4):235-241. Kösters JP, et al. Cochrane Database Syst Rev. 2003;(2):CD003373. Barlow WE et al. J Natl Cancer Inst 2002;94:1151-1159


III. Clinical Breast Examination Is an Integrated Part of the Visit • Clinical breast e examination amination is not cost-effective cost effecti e Study

n

All Cancers

Cancers Detected by CBE

Kriege, 2004

Prospective cohort (MRISC)

1909 high risk women

51

1 (only)

Warner, 2004

Prospective cohort

236 mutation carriers

22

2 (also on MRI)

Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Warner E, et al. JAMA 2004;292(11):1317-1325.


IV. Yearly Mammography 30-60 Years Mammography 60-75 Years: 2-Year Interval • Mammography is the only screening modality, resulting in mortality reduction • Reluctance to perform X-Mammo in young mutation carriers: – BRCA-genes g are onco-suppressor pp genes g and involved in DNA-reparation – Dense fibroglandular tissue

Nelson HD, et al. Ann Intern Med. 2009;151(10):727-737.


BRCA1, 29 years old, palpable l bl mass, nott suspicious i i Ultrasound: Sagital projection: Shape round/oval Margins: well well-defined defined Orientation: parallel Transverse projection: Microlobulations Not typical for a fibroadenoma, Invasive ductal carcinoma


IV. Yearly Mammography 30-60 Years Mammography 60-75 Years: 2-year Interval • Mammography is better in detection DCIS MLO R

49 years, BRCA1 Punctate MC, different in size, not a real cluster PA: DCIS Grade III

Kriege M, et al. N Eng J Med. 2004;351(5):427-437.


IV. Yearly Mammography 30-60 Years Mammography 60-75 Years: 2-Year Interval • Mammography is helpful in the interpretation of MRI

Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Nelson HD, et al. Ann Intern Med. 2009;151:727-737.


V. Yearly y MRI 25-60 Years • Systematic review of 5 (pooled) studies: – Sensitivity of X-Mammo 58% – Sensitivity of X-Mammo and MRI 94%

• Cancers found with MRI: – Less lymph node involvement: 6% vs 44% – Smaller: 6 mm vs 22 mm

Lord SJ, et al. Eur J Cancer. 2007;43(13):1905-1917. Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Chereau E, et al. Clin Breast Cancer. 10(2):113-118.


51 years old mutation t ti carrier: i 75% fibroglandular tissue Biopsy: sclerosing adenosis MC: course, punctate and amorph


7mm IDC, Grade II ER/PR +, HER2 – Node -


V. Yearly y MRI 25-60 Years • Systematic review of 5 studies: – Sensitivity of X-Mammo 58% – Sensitivity of X-Mammo and MRI 94%

• Cancers found with MRI: – less lymph node involvement: 6% vs 44% – smaller: 6 mm vs 22 mm

• False positives: x 3 – 71-74 recalls/1000 screens – 7- 46 biopsies/1000 screens Lord SJ, et al. Eur J Cancer. 2007;43(13):1905-1917. Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Chereau E, et al. Clin Breast Cancer. 10(2):113-118.


43-years-old BRCA 2 no symptoms


Enhancing g mass: Shape: Round/oval Margins: Well-defined Enhancement: Intermediate with non-enhancing septations BI-RADS BI RADS 3 Probably Fibroadenoma


CC R

BRCA 1, 1 44 years old No symptoms Ovarian carcinoma at age 24

CC L


Non mass like enhancement Distribution: ductal

BI-RADS 5, very suspicious for DCIS


Non mass like enhancement Distribution: Ductal

PA: Adenosis


CC R

BRCA 1 1, 44 years old No symptoms Ovarian carcinoma at age 24 years

CC L

Second opinion Stereotactic biopsy MC: DCIS with i i i microinvasion Planning contralateral ovariectomy


V. Yearly y MRI 25-60 Years • Always consider the menstrual cycle • MRI is not independent of breast density: – Sensitivity:

• We perform X-Mammo and MRI on the same day: – Less patient anxiety – Preference of the radiologist

• Difference in sensitivity between X-Mammo and MRI decreases with age – STOP at age 60 Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Bigenwald RZ, et al. Cancer Epid, Biomarkers & Prev. 2008;17:706-711.


V. Yearly y MRI 25-60 Years • Always consider the menstrual cycle • MRI is not independent of breast density: – Sensitivity:

and Specificity

• We perform mammography and MRI on the same day: – Less patient anxiety – Preference of the radiologist

• Difference in sensitivity between X-Mammo and MRI decreases with age – STOP at age 60 Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Bigenwald RZ, et al. Cancer Epid, Biomarkers & Prev. 2008;17:706-711.


V. Yearly y MRI 25-60 Years • Always consider the menstrual cycle • MRI is not independent of breast density: – Sensitivity:

• We perform mammography and MRI on the same day: – Less patient anxiety – Preference of the radiologist

• Difference in sensitivity between X-Mammo and MRI decreases with age – STOP at age 60 Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Bigenwald RZ, et al. Cancer Epid, Biomarkers & Prev. 2008;17:706-711.


V. Yearly y MRI 25-60 Years • Always consider the menstrual cycle • MRI is not independent of breast density: – Sensitivity:

• We perform mammography and MRI on the same day: – Less patient anxiety – Preference of the radiologist

• Difference in sensitivity between X-Mammo and MRI decreases with age – STOP at age 60 years Kriege M, et al. N Eng J Med. 2004;351(5):427-437. Bigenwald RZ, et al. Cancer Epid, Biomarkers & Prev. 2008;17:706-711.


MRI Screening and Mortality Reduction • MRI has the potential to identify breast cancer at an earlier stage, when tumors are smaller and not metastasized. • A substantial number of BRCA1 cancers are basal-phenotype p yp (Triple-): ( p ) Poor prognosis. p g Tumor size is unfortunately not prognostically relevant as it is in other types of cancer. • If 75% or more BRCA1 cancers are basalphenotype, mortality reduction will not occur.


• MRISC Population: • 599 mutation carriers • 1069 High-risk women • 489 Moderate-risk women • Overall : • Mammography sensitivity: 41.3% • MRI sensitivity: 70.7% Rijnsburger AJ, et al. J Clin Oncol. 2010 November 15 [epub ahead of print].


BRCA1 Is Different • BRCA1 has a higher proportion of: • Interval ca • Invasive ca • Unfavorable size (>2 cm) • Younger age • Rapid growth • Pushing P hi margins i • High grade • ER/PR – in 82.1% Rijnsburger AJ, et al. J Clin Oncol. 2010 November 15 [epub ahead of print].


Mortality y • 5 year cumulative overall survival: 93% • In literature: • 5 year cumulative overall survival: 74.5% 4 patients died: 3 x BRCA1, 1 x BRCA2, despite favorable tumor stage (T<1 cm N0)

Rijnsburger AJ, et al. J Clin Oncol. 2010 November 15 [epub ahead of print].


Conclusion • Surveillance in specialized p centers • CBE

25-60 years

• Yearly MRI

25-60 25 60 years

• Yearly Mammography

30-60 years

• 2-Yr interval Mammography 60-75 years • Age 75

STOP, symptomatic

• Pregnancy & breast feeding symptomatic • After preventive mastectomy symptomatic Nationaal Borstkanker Overleg (NABON). Richtlijn behandeling van het mammacarcinoom. 2008. Available at: www.oncoline.nl. Accessed November 9, 2010.


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