Prevalence of BRCA2 mutations and other clinical characteristics in women with triple-negative breast cancer.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 160-160
Author(s):  
Jennifer Chun ◽  
Freya Ruth Schnabel ◽  
Shira Schwartz ◽  
Jessica Billig ◽  
Karen Hiotis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Clinical Characteristics ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Personal History ◽  
Breast Cancers ◽  
History Of ◽  
Brca2 Mutations

160 Background: Triple-negative breast cancers (TNBC) represent 10%–20% of invasive breast cancers. Current guidelines recommend genetic testing for women who are diagnosed with TNBC. Studies have shown that BRCA1 mutations are associated with TNBC, but there is little information on the relationship of BRCA2 mutations and TNBC. The purpose of this study was to look at the clinical characteristics of TNBC compared to non-TNBC in a cohort of women with newly diagnosed breast cancer. Methods: The Breast Cancer Database at our institution was queried for patients with invasive breast cancer. We included the following variables: age, race, BRCA1,2, tumor characteristics, and personal history of breast cancer (PHBC). Statistical analyses included Pearson’s Chi-Square and Fisher’s Exact Tests. Results: Out of a total of 1,332 women, 125 (9%) had TNBC. The median age for both TNBC and non-TNBC was 59 years. Majority of women had early stage breast cancer (92%) with ductal carcinoma (80%). There was a significantly higher proportion of Blacks and Asians with TNBC (p < 0.0001). Women with TNBC had higher Ki-67 (p < 0.0001). Within the TNBC group, there were 12 (29%) patients who tested positive for BRCA1,2 mutation and 23 (8%) who tested positive for BRCA 1,2 mutations in the non-TNBC group. Interestingly, BRCA1 was not associated with TNBC (p = 0.40) and BRCA2 was significantly associated with TNBC (p < 0.0001). We also found a higher proportion of TNBC in women who had a PHBC (p = 0.01). Conclusions: In our study, women with TNBC were similar in age to women who did not have TNBC. We found that the women with TNBC in our cohort had elevated rates of BRCA2 mutations. We also found that women with a personal history of breast cancer were at risk for developing TNBC. This may be related to the use of hormonal therapy that reduces the risk of ER/PR-positive tumors. Women of all ages are at risk for developing TNBC and older age at TNBC should not deter from genetic testing.

scholarly journals Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2506
Author(s):  
Mark van Barele ◽  
Bernadette A. M. Heemskerk-Gerritsen ◽  
Yvonne V. Louwers ◽  
Mijntje B. Vastbinder ◽  
John W. M. Martens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Hormone Replacement ◽  
Breast Cancers ◽  
Younger Women ◽  
Alternative Pathways ◽  
Increased Risk ◽  
History Of ◽  
Hormone Sensitive

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.

Pathologic characteristics of breast cancer with special emphasis on prevalence of triple-negative breast cancer from Kenya: A 4-year experience.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 35-35
Author(s):  
S. Sayed ◽  
Z. Moloo ◽  
S. Mukono ◽  
R. Wasike ◽  
R. R. Chauhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Significant Proportion ◽  
Small Sample ◽  
University Hospital ◽  
Breast Cancers ◽  
Grade 3

35 Background: Previous sub classification of breast cancer in Kenya has been fraught by small sample size, non uniform staining methodology and lack of independent review. Triple Negative Breast Cancer (TNBC) is a “special interest” cancer since it represents a significant proportion of breast cancer patients and is associated with a poorer prognosis. We aimed to determine the estrogen receptor (ER), progesterone receptor (PR) and Her2/neu receptor characteristics of breast cancers and the prevalence of TNBC diagnosed at Aga Khan University Hospital, Nairobi (AKUHN) between 2007 to date. Methods: Slides and blocks of archived invasive breast cancers diagnosed at AKUHN were identified, retrieved and reviewed by two independent pathologists. Histological type, grade and pathological stage were documented. Representative sections from available blocks were stained for ER, PR, Her2 with appropriate internal controls. Scores for ER/PR were interpreted based on the ALLRED system, Her2 /neu scoring followed CAP guidelines. The initial 111 cases were validated and confirmed at Sunnybrook Health Sciences Centre, Toronto. Results: 456 cases of invasive breast cancers were diagnosed at AKUHN during the study period. 91% of cases were invasive ductal carcinomas (NOS).The rest were special types. 37% of the tumors were grade 3 and 63% were grade 2. Blocks for 318 of 456 cases were available for receptor analysis. 54% were ER and/or PR positive, with 52% of these in women < 50 yrs. 86% of the ER and/or PR positive tumors were grade 2. Only 12% were Her2/neu positive. Of the 318 cases studied, 111 (32%) were identified as TNBC. Median age was 53 yrs. 88% were grade 3. Conclusions: Invasive ductal carcinoma (NOS) was the most common breast cancer in our study. Nearly half of our cases were ER and/or PR positive and a third were TNBC. Both occurred predominantly in women less than 50 yrs. This represents the largest validated pathologic sub classification of breast cancer from a tertiary academic hospital in Kenya. Expansion of this study to encompass all breast cancers diagnosed in Kenya is underway.

scholarly journals Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant

2020 ◽  
Vol 52 (3) ◽  
pp. 680-688
Author(s):  
Hyung Seok Park ◽  
Jai Min Ryu ◽  
Ji Soo Park ◽  
Seock-Ah Im ◽  
So-Youn Jung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Triple Negative ◽  
Cumulative Risk ◽  
Pathogenic Mutation ◽  
Personal History ◽  
Clinicopathologic Characteristics ◽  
Significant Difference ◽  
History Of ◽  
Risk Reducing

PurposeRecent studies revealed the <i>BRCA1</i> c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other <i>BRCA1</i>/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data.Materials and MethodsThe data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study.ResultsThe median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with <i>BRCA1</i> carriers and showed higher penetrance of OC than patients with other <i>BRCA1</i> mutations.ConclusionL1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

scholarly journals Barriers and Opportunities in Genetic Testing for BRCA Gene Mutations in Europe: A Strategic Policy Response to Support Women and Families At Risk for Breast Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 141s-141s
Author(s):  
S. Ahmed ◽  
J. Tate ◽  
M. Thrift-Perry ◽  
S. Wait
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Triple Negative ◽  
Unmet Needs ◽  
Gene Mutations ◽  
Cancer Control ◽  
Brca Mutations ◽  
Brca Gene ◽  
Brca Genetic Testing

Background and context: An estimated 12.5% of women are at risk for breast cancer. 5%-10% of these cases are hereditary, and of these, 20%-25% are due to BRCA gene mutations. Women with BRCA mutations are at higher risk of early onset, recurrence and of triple-negative breast cancer, with fewer treatment options. These women need to be supported to seek genetic testing as early as possible. They also need support and guidance to inform family members, consider preventive interventions and obtain appropriate care and counseling. Aim: To provide an overview of the BRCA genetic testing policy landscape in Europe and highlight barriers to women and their families to access testing, information and support. Strategy: A pragmatic review of international published and gray literature. With a focus on Europe and Israel, we looked for epidemiologic data in six countries and assessed the systems, policies and services in place for genetic testing, counseling and care. This was complemented by semistructured telephone interviews with healthcare professionals, researchers and patient representatives. Policy process: We must develop comprehensive cancer control plans that provide for high-quality prevention, treatment and care for all women with BRCA mutations, whether they develop breast cancer. The unmet needs of later-stage and more difficult-to-treat breast cancers, such as BRCA-mutated or triple-negative must not be neglected. Outcomes: Current BRCA genetic testing guidelines are insufficient. Testing eligibility is restricted to high-risk patients, despite evidence that over half of women diagnosed with BRCA-related breast cancer could be missed with this approach. Access barriers to information and services include: too few genetic counselors to provide information and support to women and their families; limited primary care genetics knowledge which may lead to low referral rates and unequal testing access based on region, age and race. Individuals may also forego testing for fear of discrimination by employers or insurance companies or the effect a positive test might have on families and relationships. What was learned: Opportunities to address the unmet needs of women considering BRCA genetic testing include: greater public awareness and understanding of testing; building professional capacity to better support those getting tested and policies to protect women against discrimination from employers or insurers. The emotional impact on women who undergo testing must also be considered, as well as the provision of appropriate information, support and care through every stage of a woman's experience. This research offers a starting point for discussion with policymakers and patient organizations to ensure pathways and policies are place which integrate the patient experience into comprehensive care pathways and national cancer control plans.

The incidence of BRCA1 and BRCA2 variants of unknown significance varies in different ethnic populations

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10002-10002 ◽  
Author(s):  
D. M. Opatt ◽  
M. Morrow ◽  
M. Daly
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Genetic Testing ◽  
African American Women ◽  
White Women ◽  
Personal History ◽  
Brca1 And Brca2 ◽  
Variants Of Unknown Significance ◽  
Unknown Significance ◽  
History Of

10002 Background: BRCA1 and BRCA2 mutations in the general population are rare. Women with these mutations have a significantly increased risk of invasive breast and ovarian cancer (65–85% and 15–65% cumulative lifetime risk, respectively). Variants of unknown significance (VUS), which are of uncertain clinical importance, account for up to 50% of all identified BRCA1 and BRCA2 sequence alterations1. Methods: Pooled data from all patients presenting to Fox Chase Cancer Center for genetic counseling was examined. Patients underwent genetic testing after detailed genetic counseling. Clinical data, including gender, ethnic background, and personal history of cancer, and total number of patients tested were collected. Results: A total of 1,765 women and 236 men underwent genetic testing. The distribution of ethnicity was: <1% Asian, 2.7% African American, <1% Hispanic, 2.4% other or of more than one ethnicity, 83% White, and 11% unknown. Mutations of BRCA1 and BRCA2 were seen in 13% of the women and 2.7% of the men. VUS were seen in 6.2% of the women and .15% of the men. Of the women positive for a VUS, 2.4% were Asian, 18.1% were African American, 5.5% were Hispanic, 4.7% were more than one ethnicity, 66.9% were White, and 2.4% were Unknown ethnicity. Only .15% of the men tested were positive for a VUS, all of whom were White. Of the 51 African American women tested, 45.1% were positive for a VUS while only 5.5% of the 1,503 White women tested were positive (p<0.0001). Of the females testing positive for a VUS, a personal history of breast cancer was seen in 66.7% of Asians, 78.3% of African Americans, 100% of Hispanics, 83.3% of those more than one race, 61% of Whites, and none of the people of unknown ethnic origin. One of three men testing positive for a VUS reported a history of breast cancer. Conclusions: Identification of VUS occurred disproportionately in African Americans, occurring ten times more often in African American women than White women in our study. Studies to improve classification of VUS as deleterious or neutral are needed to enhance the utility of genetic testing for women at risk, particularly those of African American ethnicity. 1Goldman, DE et al. Am. J. Hum. Genet., 2004. No significant financial relationships to disclose.

scholarly journals Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22226-e22226
Author(s):  
A. Kwong ◽  
L. Wong ◽  
C. Wong ◽  
F. Law ◽  
E. Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
High Risk ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
History Of ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

e22226 Background: Breast cancers due to underlying germline BRCA1 and BRCA2 mutations are associated with particular pathological features that may differ from sporadic breast cancers. We report clinical and pathologic characteristics of breast cancer in a clinical cohort of high risk Chinese women with BRCA mutations and those without mutations. Methods: 202 high risk women based on their age and family history were recruited from March 2007 to November 2008. Medical information was prospectively collected from the patients and medical records. BRCA1 and BRCA2 mutations were detected using full gene sequencing and multiplex ligation-dependent probe amplification (MLPA). Results: Of the 202 female probands tested, 25 (12.3 %) were BRCA mutation carriers of which 11 (44%) were BRCA1 and 14 (56%) were BRCA2 mutations. Breast cancer risk factors, other than family history, did not differ between carriers and non-carriers. Mutation carriers were more likely to have a familial history of breast cancer (p=0.07) and personal and family history of ovarian cancer (p=0.005; p=0.007). Other cancers found in carriers families included pancreatic, gastric, colon, lung, liver, and nasopharyngeal. 23% of women diagnosed with DCIS had BRCA mutations compared with 11.4% of those with invasive cancers. BRCA related tumors were more likely to be ER, PR and Her-2 negative (Triple negative, TN) (p= 0.006). Overall 9.6% of non-BRCA cancers were TN whereas 25.9% of BRCA cancers were TN. Prevalence of TN in BRCA1 carriers is 71% compared with 13.4% in BRCA2 carriers. BRCA1 mutation related cancers were significantly more likely to be ER negative than BRCA2 and this is only significant in those who are under 40 years of age (p=0.070). Conclusions: We have a high BRCA2 mutation rate in our cohort. BRCA related breast cancer is associated with families with increasing number of first degree relatives with breast and/or ovarian cancers and were higher for DCIS cancers. Prevalence of TN breast cancers was high compared to Caucasian cohorts. BRCA mutations were associated with pathologically, poor prognostic features (TN and high grade) especially in younger women. No significant financial relationships to disclose.

scholarly journals Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikmat Abdel-Razeq ◽  
Lama Abujamous ◽  
Mahmoud Abunasser ◽  
Sara Edaily ◽  
Rayan Bater
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Young Patients ◽  
Personal History ◽  
Mutation Rates ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Variant Of Uncertain Significance

AbstractBRCA1 and BRCA2 mutations are not uncommon in breast cancer patients. Western studies show that such mutations are more prevalent among younger patients. This study evaluates the prevalence of germline mutations in BRCA1 and BRCA2 among breast cancer patients diagnosed at age 40 or younger in Jordan. Blood samples of patients with breast cancer diagnosed at age 40 years or younger were obtained for DNA extraction and BRCA sequencing. Mutations were classified as benign/likely benign (non-carrier), pathogenic/likely pathogenic variant (carrier) and variant of uncertain significance (VUS). Genetic testing and counseling were completed on 616 eligible patients. Among the whole group, 75 (12.2%) had pathogenic or likely pathogenic variants; two of the BRCA2 mutations were novel. In multivariate analysis, triple-negative disease (Odd Ratio [OR]: 5.37; 95% CI 2.88–10.02, P < 0.0001), breast cancer in ≥ 2 family members (OR: 4.44; 95% CI 2.52–7.84, P < 0.0001), and a personal history ≥ 2 primary breast cancers (OR: 3.43; 95% CI 1.62–7.24, P = 0.001) were associated with higher mutation rates. In conclusion, among young Jordanian patients with breast cancer, mutation rates are significantly higher in patients with triple-negative disease, personal history of breast cancer and those with two or more close relatives with breast cancer.

Impact of bilateral oophorectomy on contralateral breast cancer risk in BRCA negative women from site-specific hereditary breast cancer kindreds.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1511-1511
Author(s):  
Kara C Long ◽  
Malcolm C Pike ◽  
Ebunoluwa Otegbeye ◽  
Angela G. Arnold ◽  
Zsofia Kinga Stadler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Hereditary Breast Cancer ◽  
Personal History ◽  
Inclusion Criteria ◽  
Brca Mutations ◽  
Site Specific ◽  
History Of ◽  
Record Review ◽  
Brca Negative

1511 Background: BRCA negative (BRCAneg) women from site-specific hereditary breast cancer (SSB) kindreds have been shown to have an increased risk of breast cancer (BC), but not ovarian cancer (OC). It is hypothesized that, as in women with BRCA mutations, bilateral salpingo-oophorectomy (BSO) will decrease the risk of developing future BCs in women from these BRCAneg SSB kindreds. Methods: Since 5/1995, all women undergoing genetic counseling and testing for BRCA mutations at our institution were offered participation in an IRB-approved prospective cohort study. This sub-study examines the impact of BSO on contralateral BC risk in BRCAneg SSB kindreds. Inclusion criteria were: a personal history of unilateral invasive BC ≤ age 60, at least one 1st or 2nd degree female relative with BC ≤ age 60, testing BRCAneg between 1/1/2002 and 2/28/2011. Exclusion criteria were: bilateral mastectomy (BM) or BSO prior to genetic testing, family history of OC, <6 months of followup (F/U). Demographic data and pedigrees were collected at the start of F/U, which was defined as the date of genetic testing. F/U data was obtained via mailed questionnaire and medical record review. Participants were censored at the time of BM, OC, or last F/U. Data were analyzed using a Cox proportional-hazards model with time from genetic testing as the time variable and BSO as the time dependent covariate. Results: 328 living participants met the inclusion criteria and F/U was obtained on 301 (208 via questionnaire, 93 via record review). Median age at genetic testing was 49.0 years (27.4-73.2 years). Median F/U time was 5.1 years (0.5-10.5 years). During the course of F/U, 43 women underwent BSO and 21 women underwent BM. There were 12 contralateral BCs (8 invasive, 4 DCIS) identified: 3 in the BSO group and 9 in the no-BSO group. After controlling for age, parity, prior hormone use, and estrogen receptor status of the original BC, the risk of contralateral BCs was not decreased in women who underwent BSO vs those who did not (HR 2.07, 95% CI 0.51 – 8.35, P=0.31). Conclusions: In BRCAneg women from SSB kindreds with a personal history of early onset BC, BSO does not decrease the risk of developing contralateral BC.

scholarly journals Metaplastic breast cancer with chondroid differentiation—case report and literature review

2021 ◽  
Vol 2021 (4) ◽  
Author(s):  
Cláudia Leite ◽  
Nuno Dias ◽  
Domingos Oliveira ◽  
Rita Mesquita Pinto ◽  
Francisco Cortez Vaz
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Conservative Surgery ◽  
Breast Cancers ◽  
Histological Subtypes ◽  
Breast Lump ◽  
Metaplastic Breast Cancer ◽  
Node Negative ◽  
Pathological Report

Abstract Metaplastic breast cancer (MBC) comprises less than 1% of all breast cancers, and it is defined by a mixture of adenocarcinoma plus mesenchymal and epithelial components. It is more common in older and black female patients. It has a larger size and faster growth, and it is frequently node-negative and triple-negative when compared with invasive ductal carcinoma. The authors report the case of a 72-year-old female patient, presenting with a breast lump, whose biopsy revealed a probable MBC with chondroid differentiation. She underwent a breast conservative surgery (BCS) and axillary sentinel lymph node dissection (SLND). The pathological report was concordant with the biopsy, and the patient was proposed to chemoradiotherapy. Despite its rarity and more severe features at diagnosis, BCS plus SLND plus radiotherapy should be offered to these patients, associated with chemotherapy. Chondroid differentiation is the rarest of all histological subtypes.

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