Mutation Analysis of BRCA1 and BRCA2 in Italian Hereditary and Sporadic Forms of Breast and Ovarian Cancers: Tumor Genotype-Phenotype Correlation in Breast Cancer BRCA-Mutation Carriers

10014 Background: Several large observational studies have demonstrated that magnetic resonance imaging (MRI) is much more sensitive than M (sensitivity 71–96% vs. 28–43%) for screening women > age 25 at high risk for hereditary breast cancer. However, MRI is much more costly and less specific than M. The extent to which the low sensitivity of M in these studies is due to the greater average breast density of younger women is unknown. Accordingly, we sought to determine the sensitivity of M and MRI according to breast density for the detection of breast cancer in a screening study of BRCA mutation carriers. Methods: Breast density was measured on the screening mammogram of the contralateral breast for all women who developed in-situ or invasive breast cancer on study. Density was measured in 2 ways: qualitatively according to the four categories characterized by the BIRADS system: 1) mostly fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, 4) extremely dense; and semi-quantitatively using computer-aided techniques with subsequent classification as: A) ≤10%, B) 11–25%, C) 26%-50%, or D) >50% density. Results: Between 11/97 and 06/05 a total of 39 cases (12 in-situ and 27 invasive) were found in 36 mutation carriers (19 BRCA1 and 17 BRCA2). Mean age of the women with cancer was 48 (range 34 to 64). Average semi-quantitative breast density for BRCA1 mutation carriers was 28% and for BRCA2 was 27%. Sensitivity of M vs. MRI for in-situ cases was 25% vs. 83%, and for invasive cases was 30% vs. 93%. Sensitivities for BRCA1 and BRCA2 mutation carriers were similar. For BIRADS 1 to 4 respectively M detected 1/3 (33%), 5/11 (45%), 4/22 (18%), and 1/3 (33%) of cases; and for density groups A to D respectively detected 2/6 (33%), 7/15 (47%), 1/11 (9%) and, 1/7 (14%). Conclusion: Although there was a trend towards decreasing mammographic sensitivity with increasing density, even among BRCA mutation carriers with low breast density mammography is an inadequate screening tool. No significant financial relationships to disclose.

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Therapeutic radiation for breast cancer in BRCA mutation carriers and contralateral breast cancer (CBC) risk

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.611 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 611-611

Author(s):

H. C. Moore ◽

R. Wesolowski ◽

T. K. Choueiri ◽

L. Rybicki ◽

A. G. Shealy ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Treatment ◽

Brca Mutation ◽

Negative Group ◽

Breast Cancer Patients ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Mutation Carriers ◽

Brca Mutation Carriers

611 Background: BRCA mutation carriers diagnosed with breast cancer are at high risk for contralateral second primary breast cancers. Mutations in BRCA1 and BRCA2 lead to defects in DNA repair. Radiation treatment for breast cancer is felt to increase risk of CBC, but the interaction between BRCA status and local radiation therapy with respect to their effects on CBC is unclear. Methods: Through an IRB approved database registry at the Cleveland Clinic, breast cancer patients tested for BRCA1 and BRCA2 mutations were identified and evaluated for CBC events and radiation treatment history. Patients with inadequate clinical follow-up, those with bilateral synchronous breast cancer and those undergoing bilateral mastectomy within one year of the original breast cancer diagnosis were excluded from the analysis. Chi-square test was used to compare CBC rates with or without prior radiation separately in patients testing positive and those testing negative for BRCA mutations. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 57 met the inclusion criteria. Twenty-one carried BRCA1 or BRCA2 mutations and 36 tested negative for these mutations. Median follow-up for the two groups was 69.5 months (92 months in BRCA positive group and 51.5 months in BRCA negative group). Median age at diagnosis was 45 years (41 years in BRCA positive group and 48.5 in BRCA negative group). Among the 21 carriers, 9 patients (43%) developed CBC while only 3 of 36 patients (8%) testing negative for BRCA mutations developed CBC. Thirteen of 21 mutation carriers (62%) had received radiation treatment for the original cancer: CBC occurred in 3 of 13 (23%) radiated patients and 6 of 8 (75%) patients who had not received radiation (p= 0.02). Among 36 patients with negative BRCA testing, 30 (83%) had received radiation: CBC occurred in 3 of 30 (10%) mutation negative patients who had received prior radiation and in 0 of the 6 patients who had not received radiation (p = 0.42). Conclusions: CBC incidence was higher among BRCA mutation carriers than a control group suspected of having hereditary breast cancer but testing negative for these mutations. The use of radiation in the presence of a BRCA mutation, however, does not appear to further increase the risk for CBC. No significant financial relationships to disclose.

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Reply to the Comments on “Radiation induced breast cancer risk in BRCA mutation carriers from low-dose radiological exposures: a systematic review”

Radioprotection ◽

10.1051/radiopro/2018004 ◽

2018 ◽

Vol 53 (1) ◽

pp. 69-71

Author(s):

C. Colin ◽

N. Foray ◽

G. Di Leo ◽

F. Sardanelli

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Low Dose ◽

Brca Mutation ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

Radiation Induced

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Costs of breast cancer surveillance in BRCA mutation carriers

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)70477-4 ◽

2008 ◽

Vol 6 (7) ◽

pp. 94-95

Author(s):

Y.J.L. Kamm ◽

C. Boetes ◽

E.M.M. Adang ◽

P. Bull ◽

H.J. Bonenkamp ◽

...

Keyword(s):

Breast Cancer ◽

Brca Mutation ◽

Cancer Surveillance ◽

Mutation Carriers ◽

Brca Mutation Carriers

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Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer

Annals of Oncology ◽

10.1093/annonc/mdy515 ◽

2019 ◽

Vol 30 (3) ◽

pp. 412-417 ◽

Cited By ~ 8

Author(s):

E. Evron ◽

A.M. Ben-David ◽

H. Goldberg ◽

G. Fried ◽

B. Kaufman ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Brca Mutation ◽

Contralateral Breast ◽

Early Stage Breast Cancer ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

Prophylactic Irradiation

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Management Options after Prophylactic Surgeries in Women with BRCA Mutations: A Review

Cancer Control ◽

10.1177/107327480701400403 ◽

2007 ◽

Vol 14 (4) ◽

pp. 330-337 ◽

Cited By ~ 4

Author(s):

Dawn C. Allain ◽

Kevin Sweet ◽

Doreen M. Agnese

Keyword(s):

Medical Management ◽

Cancer Susceptibility ◽

Brca Mutation ◽

Brca2 Gene ◽

Brca1 And Brca2 ◽

Management Options ◽

Cancer Susceptibility Genes ◽

Mutation Carriers ◽

Increased Risk ◽

Brca Mutation Carriers

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

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