scholarly journals RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3251
Author(s):  
Gina Reye ◽  
Xuan Huang ◽  
Kara L. Britt ◽  
Christoph Meinert ◽  
Tony Blick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mammographic Density ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Brca2 Gene ◽  
Mammary Tissue ◽  
Tissue Stiffness ◽  
Mutation Carriers

High mammographic density (MD) increases breast cancer (BC) risk and creates a stiff tissue environment. BC risk is also increased in BRCA1/2 gene mutation carriers, which may be in part due to genetic disruption of the tumour suppressor gene Ras association domain family member 1 (RASSF1A), a gene that is also directly regulated by tissue stiffness. High MD combined with BRCA1/2 mutations further increase breast cancer risk, yet BRCA1/2 mutations alone or in combination do not increase MD. The molecular basis for this additive effect therefore remains unclear. We studied the interplay between MD, stiffness, and BRCA1/2 mutation status in human mammary tissue obtained after prophylactic mastectomy from women at risk of developing BC. Our results demonstrate that RASSF1A expression increased in MCF10DCIS.com cell cultures with matrix stiffness up until ranges corresponding with BiRADs 4 stiffnesses (~16 kPa), but decreased in higher stiffnesses approaching malignancy levels (>50 kPa). Similarly, higher RASSF1A protein was seen in these cells when co-cultivated with high MD tissue in murine biochambers. Conversely, local stiffness, as measured by collagen I versus III abundance, repressed RASSF1A protein expression in BRCA1, but not BRCA2 gene mutated tissues; regional density as measured radiographically repressed RASSF1A in both BRCA1/2 mutated tissues. The combinatory effect of high MD and BRCA mutations on breast cancer risk may be due to RASSF1A gene repression in regions of increased tissue stiffness.

Mammographic density and breast cancer risk in germline BRCA1/2 mutation-carriers

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 9677-9677
Author(s):  
G. Mitchell ◽  
R. Warren ◽  
R. Davies ◽  
J. Brown ◽  
P. Susan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mammographic Density ◽  
Mutation Carriers

Breast tumor location in BRCA mutation carriers and implications for prevention.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13048-e13048
Author(s):  
Ava Hosseini ◽  
Laura Esserman ◽  
Anne M. Wallace ◽  
Amal Khoury ◽  
Alfred Au ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca Mutation ◽  
Tumor Location ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Outer Quadrant ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

e13048 Background: Although pathogenic mutations in the BRCA gene are known to confer a high risk of breast cancer, close to 65% of mutation carriers do not opt for prophylactic mastectomy. These women are managed with intense screening, which does not aid in prevention. Breast reduction mammoplasty is a surgical technique shown to reduce breast cancer risk (0.39-0.61 relative risk reduction), and can be modified to target specific areas of the breast. Given that most sporadic breast cancers involve the upper outer quadrant, we wondered if a majority of tumors in BRCA mutation carriers would also be confined to one quadrant, or if they would be equally distributed throughout the breast given the high baseline risk present. Identifying a particularly high risk area of the breast could potentially allow for the use of targeted cosmetic mammoplasty as a novel method of risk reduction. Methods: We reviewed imaging reports on 103 consecutive patients with BRCA mutations and invasive breast cancer, and categorized tumor location by quadrant. Tumors spanning > 1 quadrant were classified as being in both. Bilateral cancers were counted separately. Categorical variables were compared with the chi-squared test. Results: Mean age at breast cancer diagnosis was 44 years. Mean tumor size was 2.2 cm (0.1-7cm) with mean distance from the nipple of 4.8 cm (1-12 cm). 92% of tumors were invasive ductal carcinoma, 46% were hormone receptor positive, 10% Her2 positive, and 44% triple negative. 70% of the tumors were unicentric. Tumors were significantly more likely to be in the upper outer quadrant (54%, with the other quadrants having 11-17% of tumors respectively) whether or not multicentric tumors were included in the analysis (p < 0.00001). Her2 positive tumors were more likely to be multicentric than other subtypes (p = 0.021). Conclusions: More than half of breast cancers in BRCA mutation carriers form in the upper outer quadrant, suggesting that breast reduction mammoplasty targeting removal of the upper outer quadrant could significantly reduce breast cancer risk. For those women who choose not to have prophylactic mastectomies or are not yet ready, these data support an intermediate step to help decrease breast cancer risk, which warrants further study.

Fertility treatments and breast cancer risk in Jewish Israeli BRCA mutation carriers

2021 ◽  
Author(s):  
Tamar Perri ◽  
Shani Naor-Revel ◽  
Perry Eliassi-Revivo ◽  
Dror Lifshitz ◽  
Eitan Friedman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca Mutation ◽  
Fertility Treatments ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

Bilateral Prophylactic Mastectomy Reduces Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group

2004 ◽  
Vol 22 (6) ◽  
pp. 1055-1062 ◽  
Author(s):  
Timothy R. Rebbeck ◽  
Tara Friebel ◽  
Henry T. Lynch ◽  
Susan L. Neuhausen ◽  
Laura van ’t Veer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Prophylactic Mastectomy ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Bilateral Prophylactic Mastectomy ◽  
Breast Cancer Risk Reduction ◽  
Cancer Risk Reduction

Purpose Data on the efficacy of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations are limited, despite the clinical use of this risk-management strategy. Thus, we estimated the degree of breast cancer risk reduction after surgery in women who carry these mutations. Patients and Methods Four hundred eighty-three women with disease-associated germline BRCA1/2 mutations were studied for the occurrence of breast cancer. Cases were mutation carriers who underwent bilateral prophylactic mastectomy and who were followed prospectively from the time of their center ascertainment and their surgery, with analyses performed for both follow-up periods. Controls were BRCA1/2 mutation carriers with no history of bilateral prophylactic mastectomy matched to cases on gene, center, and year of birth. Both cases and controls were excluded for previous or concurrent diagnosis of breast cancer. Analyses were adjusted for duration of endogenous ovarian hormone exposure, including age at bilateral prophylactic oophorectomy if applicable. Results Breast cancer was diagnosed in two (1.9%) of 105 women who had bilateral prophylactic mastectomy and in 184 (48.7%) of 378 matched controls who did not have the procedure, with a mean follow-up of 6.4 years. Bilateral prophylactic mastectomy reduced the risk of breast cancer by approximately 95% in women with prior or concurrent bilateral prophylactic oophorectomy and by approximately 90% in women with intact ovaries. Conclusion Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1/2 mutations by approximately 90%.

scholarly journals Mammographic Density and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

2006 ◽  
Vol 66 (3) ◽  
pp. 1866-1872 ◽  
Author(s):  
Gillian Mitchell ◽  
Antonis C. Antoniou ◽  
Ruth Warren ◽  
Susan Peock ◽  
Judith Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mammographic Density ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Mutation Carriers
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