Expanding the Criteria for <i>BRCA</i> Mutation Testing in Breast Cancer Survivors

Kwon, Janice S.; Gutierrez‐Barrera, Angelica M.; Young, Diana; Sun, Charlotte C.; Daniels, Molly S.; Lu, Karen H.; Arun, Banu K.

doi:10.1200/jco.2010.28.0719

Cited by 123 publications

(147 citation statements)

References 71 publications

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“…1,2 Known mutations in the breast cancer susceptibility genes BRCA1 or BRCA2 account for more than 50% of these hereditary breast cancers. 3 Carriers of heterozygous germline mutations in the BRCA1 or BRCA2 genes have approximately a 2% to 3% yearly risk of developing breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience

Arun

Bayraktar

Liu

et al. 2011

JCO

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158

107

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A B S T R A C T PurposeTo compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. Patients and MethodsA total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. ResultsFifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P Ͻ .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] ϭ 3.16; 95% CI, 1.55 to 6.42; P ϭ .002), estrogen receptor (ER) negativity (OR ϭ 1.96; 95% CI:1.05 to 3.65; P ϭ .03) and concurrent trastuzumab use (OR ϭ 4.18; 95% CI, 2.04 to 8.57; P Ͻ .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P ϭ .001) and OS (P ϭ .01) rates than patients who did not. ConclusionBRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers.

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Section: Introductionmentioning

confidence: 99%

Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience

Arun

Bayraktar

Liu

et al. 2011

JCO

Self Cite

158

107

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“…Our data and other studies demonstrate that these women may have a significant risk to carry a BRCA1 or BRCA2 mutation. Suggestions to adopt or expand the inclusion criteria for sporadic breast cancer patients have already been made [38]. Kwon et al [38] suggest offering genetic testing to all women with triple-negative breast cancers diagnosed before the age of 50.…”

Section: Resultsmentioning

confidence: 98%

Prevalence of BRCA1/2 mutations in sporadic breast/ovarian cancer patients and identification of a novel de novo BRCA1 mutation in a patient diagnosed with late onset breast and ovarian cancer: implications for genetic testing

Leeneer

Coene

Crombez

et al. 2011

Breast Cancer Res Treat

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In order to adequately evaluate the clinical relevance of genetic testing in sporadic breast and ovarian cancer patients, we offered comprehensive BRCA1/2 mutation analysis in patients without a family history for the disease. We evaluated the complete coding and splice site regions of BRCA1/2 in 193 sporadic patients. In addition, a de novo mutation was further investigated with ultra deep sequencing and microsatellite marker analysis. In 17 patients (8.8%), a deleterious germline BRCA1/2 mutation was identified. The highest mutation detection ratio (3/7 = 42.9%) was obtained in sporadic patients diagnosed with breast and ovarian cancer after the age of 40. In 21 bilateral breast cancer patients, two mutations were identified (9.5%). Furthermore, 140 sporadic patients with unilateral breast cancer were investigated. Mutations were only identified in patients diagnosed with breast cancer before the age of 40 (12/128 = 9.4% vs. 0/12 with Dx > 40). No mutations were detected in 17 sporadic male breast cancer and 6 ovarian cancer patients. BRCA1 c.3494_3495delTT was identified in a patient diagnosed with breast and ovarian cancer at the age of 52 and 53, respectively, and was proven to have occurred de novo at the paternal allele. Our study shows that the mutation detection probability in specific patient subsets can be significant, therefore mutation analysis should be considered in sporadic patients. As a consequence, a family history for the disease and an early age of onset should not be used as the only criteria for mutation analysis of BRCA1/2. The relatively high mutation detection ratio suggests that the prevalence of BRCA1/2 may be underestimated, especially in sporadic patients who developed breast and ovarian cancer. In addition, although rare, the possibility of a de novo occurrence in a sporadic patient should be considered.

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“…Novel chemotherapeutic regimens (e.g., platinum agents) and biologics (e.g., poly(ADP-ribose) polymerase (PARP) inhibitors) that have shown promise in women with early and advanced disease may also be particularly relevant in the treatment of premenopausal women with ER-negative disease, given that this population is more likely to develop triple-negative disease and also more likely to harbor a BRCA1 or BRCA2 germline mutation [28][29][30][31].…”

Section: Chemotherapy Selection For Premenopausal Womenmentioning

confidence: 99%

Chemotherapy in Premenopausal Breast Cancer Patients

Partridge

2015

Breast Care

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Evidence has long demonstrated that premenopausal women obtain the greatest benefit from adjuvant chemotherapy overall, with risk reduction increasing with decreasing age. The chemoendocrine effect of chemotherapy has only more recently been documented as impacting on outcomes for women with hormone receptor-positive breast cancer, and recent data have elucidated the optimal strategies for manipulating the menopausal status to improve disease outcomes, without necessarily including cytotoxic chemotherapy. Still, many premenopausal women will require adjuvant cytotoxic chemotherapy, and the effects of treatment on women diagnosed with breast cancer in the premenopausal setting can have important implications both on their breast cancer outcomes and on comorbidities and psychosocial outcomes. This article describes the most recent information and issues surrounding the indications, effects, and special considerations for adjuvant chemotherapy in premenopausal women with breast cancer, in an effort to inform their care.

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Expanding the Criteria for BRCA Mutation Testing in Breast Cancer Survivors

Abstract: Testing women with TN breast cancers who were younger than 50 years for BRCA mutations is a cost-effective strategy and should be adopted into current guidelines for genetic testing.

Cited by 123 publications

References 71 publications

Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience

Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience

Prevalence of BRCA1/2 mutations in sporadic breast/ovarian cancer patients and identification of a novel de novo BRCA1 mutation in a patient diagnosed with late onset breast and ovarian cancer: implications for genetic testing

Chemotherapy in Premenopausal Breast Cancer Patients

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