Clinical and Pathologic Characteristics of Patients With BRCA-Positive and BRCA-Negative Breast Cancer

Purpose Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. Patients and Methods Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. Results Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). Conclusion These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non–triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.

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Frequency of Triple-Negative Breast Cancer in BRCA1 Mutation Carriers: Comparison Between Common Ashkenazi Jewish and Other Mutations

Journal of Clinical Oncology ◽

10.1200/jco.2012.44.5635 ◽

2012 ◽

Vol 30 (35) ◽

pp. 4447-4448 ◽

Cited By ~ 7

Author(s):

Nadine Tung ◽

Judy E. Garber ◽

Anne Lincoln ◽

Susan M. Domchek

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Brca1 Mutation ◽

Ashkenazi Jewish ◽

Mutation Carriers

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Characteristics of Triple-Negative Breast Cancer in Patients With a BRCA1 Mutation: Results From a Population-Based Study of Young Women

Journal of Clinical Oncology ◽

10.1200/jco.2010.33.6446 ◽

2011 ◽

Vol 29 (33) ◽

pp. 4373-4380 ◽

Cited By ~ 71

Author(s):

Eunjung Lee ◽

Roberta McKean-Cowdin ◽

Huiyan Ma ◽

Darcy V. Spicer ◽

David Van Den Berg ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Brca1 Mutation ◽

Population Based ◽

Age At Menarche ◽

Ashkenazi Jewish ◽

Jewish Women ◽

Mutation Status ◽

Receptor Status ◽

Mutation Carriers

Purpose Triple-negative breast cancers (TNBCs) are tumors with low or no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. These tumors have a poor prognosis, remain a clinical challenge, and are more common among women with BRCA1 mutations. We tested whether there are distinguishing features of TNBC after BRCA1 mutation status has been taken into account. Patients and Methods We sequenced BRCA1 and BRCA2 genes in a population-based sample of 1,469 patients with incident breast cancer age 20 to 49 years from Los Angeles County (California). Information on tumor receptor status was available for 1,167 women. Clinical, pathologic, and hormone-related lifestyle characteristics were compared across patient subgroups defined by BRCA1 mutation status and triple-negative receptor status. Results Forty-eight percent of BRCA1 mutation carriers had TNBC compared with only 12% of noncarriers. Within BRCA1 mutation carriers, as well as within noncarriers, triple-negative receptor status was associated with younger age at diagnosis and higher tumor grade. Among women without a BRCA1 mutation, we observed that women with TNBC had higher premenopausal body mass index and earlier age at first full-term pregnancy than those with non-TNBC. Age at menarche and other reproductive factors were not associated with triple-negative status regardless of BRCA1 mutation status. Within BRCA1 mutation carriers, Ashkenazi Jewish women were about five times more likely to have TNBC than non–Ashkenazi Jewish women. Conclusion Our results suggest that among BRCA1 mutation carriers, as among noncarriers, there are unique characteristics associated with the triple-negative subtype. The findings in Ashkenazi Jewish BRCA1 mutation carriers should be confirmed.

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Clinical outcome of triple negative breast cancer in BRCA1 mutation carriers and noncarriers

Cancer ◽

10.1002/cncr.25911 ◽

2011 ◽

Vol 117 (14) ◽

pp. 3093-3100 ◽

Cited By ~ 43

Author(s):

Larissa J. Lee ◽

Brian Alexander ◽

Stuart J. Schnitt ◽

Amy Comander ◽

Bridget Gallagher ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Outcome ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Brca1 Mutation ◽

Mutation Carriers

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Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers

Breast Cancer Research and Treatment ◽

10.1007/s10549-016-3800-5 ◽

2016 ◽

Vol 157 (1) ◽

pp. 157-165 ◽

Cited By ~ 17

Author(s):

Shani Paluch-Shimon ◽

Eitan Friedman ◽

Raanan Berger ◽

Moshe Papa ◽

Maya Dadiani ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Brca1 Mutation ◽

Mutation Carriers

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Triple Negative Breast Cancer in BRCA1 Mutation Carriers With a Complete Radiologic Response to Neoadjuvant Paclitaxel: A Case Report

Clinical Breast Cancer ◽

10.1016/j.clbc.2014.08.006 ◽

2015 ◽

Vol 15 (2) ◽

pp. e155-e158 ◽

Cited By ~ 4

Author(s):

Monika L. Burness ◽

Elias I. Obeid ◽

Olufunmilayo I. Olopade

Keyword(s):

Breast Cancer ◽

Case Report ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Brca1 Mutation ◽

Mutation Carriers

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Abstract 1192: Triple negative breast cancer: BRCAness and concordance of clinical features and treatment response with BRCA1 mutation carriers.

10.1158/1538-7445.am2013-1192 ◽

2013 ◽

Author(s):

Esther H. Lips ◽

Lennart Mulder ◽

Lizet E. van der Kolk ◽

Anne M.M. Oonk ◽

Alex L.T. Imholz ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Response ◽

Clinical Features ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Brca1 Mutation ◽

Mutation Carriers

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Clinical and morphological characteristics of BRCA-associated and sporadic breast cancer in fertile female in the Altai territory.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e12560 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e12560-e12560

Author(s):

Valentina Dmitrievna Petrova ◽

Svetlana Aleksandrovna Terekhova ◽

Tatiyana Vladimirovna Sinkina ◽

Inna Anatolievna Selezneva ◽

Ylija Nikolaevna Dimitriadi ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Brca Mutation ◽

Brca1 Mutation ◽

Morphological Characteristics ◽

Young Female ◽

Brca Mutations ◽

Cancer History ◽

Fertile Female ◽

Family Cancer History

e12560 Background: Breast cancer (BC) for more than 10 years is the most frequent cancer in females in the Altai territory of Russian Federation. The share of patients under 40 years old varies from 2.6% to 16.0%. Genetically dependent nature of BC in young female is scientifically confirmed fact. The aim of this study was to analyze characteristics of BRCA-associated and sporadic BC in fertile females. Methods: 161 female patients of fertile age (under 40 years old) with BC were examined. Clinical, morphological and genetic (BRCA1) factors were analyzed. BRCA1 mutation was revealed in 22 patients (139 patients did not have it). Results: 82.0% of patients with BRCA1 mutations had positive family cancer history. In this group BC was diagnosed more frequently at the age of 31-35 y.o. (40.9%), while in the group of sporadic cancer – at the age of 36-40 y.o. (58.2%). Pathomorphological forms of BC were analyzed and in both groups infiltrative forms of BC were the most frequent (95.5% and 91.4% correspondingly). I stage cases of BC were diagnosed more frequently the group of sporadic cancers than in the group of BRCA-associated cancers (23.0% and 4.5% correspondingly, P<0.05). Hormone status of the tumours was analyzed. BRCA-associated cancers were significantly more often ER and PR negative (87.5%, P<0.05). Hyperexpression of Her2neu was not revealed in this group. In the group of patients without BRCA mutation ER and PR negative tumours were also prevalent (60.5%, P<0.05). Hyperexpression of Her2neu (+++) was revealed in 6.9%. Triple negative cancers were prevalent in the both groups, while in the group of BRCA-associated cancers there were 91.7% of such tumours. The percentage of polyneoplasia in the group of patients with BRCA mutations was higher than in the group without them (12.0 and 1.0 correspondingly, P<0.05). Conclusions: In females of fertile age carriage of BRCA mutations in 82.0% connected with family cancer history. In the group of sporadic cancers I stage cases of BC are more frequent. In both groups hormone receptor negative and triple negative cancer are prevalent, but in the group of BRCA-associated cancers the percentage of such tomours and polyneoplasia are significantly higher.

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Current Status of Poly(ADP-ribose) Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer

International Journal of Breast Cancer ◽

10.1155/2012/829315 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

David J. Hiller ◽

Quyen D. Chu

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Expression Patterns ◽

Progesterone Receptors ◽

Parp Inhibitors ◽

Current Status ◽

Brca Mutations ◽

Basal Like Breast Cancer ◽

Her 2

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that is clinically defined as lacking estrogen and progesterone receptors, as well as being ERBB2 (HER-2) negative. Without specific therapeutic targets, TNBC carries a worse prognosis than other types of breast cancer in the absence of therapy. Research has now further differentiated breast cancer into subtypes based on genetic expression patterns. One of these subtypes, basal-like, frequently overlaps with the clinical picture of TNBC. Additionally, both TNBC and basal-like breast cancer link to BRCA mutations. Recent pharmaceutical advances have created a class of drugs, poly(ADP-ribose) polymerase (PARP) inhibitors, which are showing potential to effectively treat these patients. The aim of this paper is to summarize the basis behind PARP inhibitors and update the current status of their development in clinical trials for the treatment of TNBC.

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