Epidemiology, biology, and treatment of triple-negative breast cancer in women of African ancestry

Triple negative breast cancer (TNBC), representing 10-15% of breast tumors diagnosed each year, is a clinically defined subtype of breast cancer associated with poor prognosis. The higher incidence of TNBC in certain populations such as young women and/or women of African ancestry and a unique pathological phenotype shared between TNBC and BRCA1-deficient tumors suggest that TNBC may be inherited through germline mutations. In this article, we describe genes and genetic elements, beyond BRCA1 and BRCA2, which have been associated with increased risk of TNBC. Multigene panel testing has identified high- and moderate-penetrance cancer predisposition genes associated with increased risk for TNBC. Development of large-scale genome-wide SNP assays coupled with genome-wide association studies (GWAS) has led to the discovery of low-penetrance TNBC-associated loci. Next-generation sequencing has identified variants in noncoding RNAs, viral integration sites, and genes in underexplored regions of the human genome that may contribute to the genetic underpinnings of TNBC. Advances in our understanding of the genetics of TNBC are driving improvements in risk assessment and patient management.

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BRCA1/2 mutation prevalence among triple-negative breast cancer patients from a large commercial testing cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1544 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1544-1544 ◽

Cited By ~ 2

Author(s):

Kristilyn Dillman Zonno ◽

Rajesh R. Kaldate ◽

Christopher Arnell ◽

Jennifer Saam ◽

Brian Abbott ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

African Ancestry ◽

Parp Inhibitors ◽

Ashkenazi Jewish ◽

Breast Cancer Patients ◽

Cancer Network ◽

Testing Criteria

1544 Background: BRCA1/2 deleterious mutation identification among triple-negative breast cancer (TNBC) patients has gained importance due to cancer-risk management implications for patients and their relatives, and also has an emerging role in guiding treatment selection for therapies such as PARP inhibitors. The National Comprehensive Cancer Network (NCCN) currently recommends BRCA1/2 testing for TNBC patients diagnosed at age <60. Mutation prevalence among TNBC patients has previously been studied only in small regionalized cohorts. A recent study in unselected patients using the updated definitive criteria for TNBC reported mutation prevalence as 10.6%. Methods: Following the 2011 NCCN Hereditary Breast and Ovarian Cancer (HBOC) Testing Criteria update, serial cohorts of > 5,000 Ashkenazi Jewish and > 65,000 non-Ashkenazi Jewish breast cancer patients undergoing commercial BRCA1/2 testing were analyzed. Age at diagnosis, ethnicity, and provider-reported TN status were obtained from test requisition forms completed by ordering providers, and correlated with test results. Neither the accuracy nor definitive criteria used for TN status reported was independently verified. Results: Incidence of TNBC was reported as 9.7% among non-Ashkenazi patients and 16.5% within the subset with African ancestry. Incidence of TNBC was reported as 4.5% among Ashkenazi patients, but this is likely affected by test ordering for this population. The Table displays the BRCA1/2mutation rates classified by ethnicity and age-group. Conclusions: This study provides the most robust estimate to date of BRCA1/2 mutation prevalence among TNBC patients of all ages. The mutation rates seen among TNBC patients diagnosed after age 60 also illustrate the importance of testing such patients who may not meet the current NCCN HBOC testing criteria. [Table: see text]

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Panoptic Overview of Triple-Negative Breast Cancer in Nigeria: Current Challenges and Promising Global Initiatives

Journal of Global Oncology ◽

10.1200/jgo.17.00116 ◽

2018 ◽

pp. 1-20

Author(s):

Nikita Wright ◽

Padmashree Rida ◽

Emad Rakha ◽

Ayodeji Agboola ◽

Ritu Aneja

Keyword(s):

Breast Cancer ◽

United States ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Resource Constraints ◽

African Ancestry ◽

Expression Patterns ◽

Tumor Biology ◽

The United States ◽

Nigerian Women

PurposeTriple-negative breast cancer (TNBC) is the most deadly form of breast cancer (BC) today. TNBC treatment is fraught with challenges because of the extensive interpatient heterogeneity in clinical behavior and scarcity of stratifying biomarkers and actionable targets. Women of African ancestry face a disproportionate burden resulting from this disease, which affects them earlier and more aggressively and has a higher propensity to spread and resist conventional treatments. A much higher proportion of Nigerian patients with BC have TNBC compared with patients with BC in the United States and Europe.MethodsThis article spotlights Nigeria as an example of a nation wherein genetic and nongenetic spheres of influence intersect to affect the prevalence of this disease, the scale of its challenge, and its toll.ResultsStudies have illuminated the inherently different tumor biology of Nigerian TNBCs, which show distinct genetic variants and gene expression patterns compared with European or European-American TNBCs. Parallels are apparent between TNBC phenotypes among African Americans and Nigerians, implicating the common thread of shared genetic ancestry between these populations. Reproductive, lifestyle, socioeconomic, and cultural factors also shape TNBC outcomes in Nigeria, as do resource constraints in Nigerian health care and research sectors.ConclusionIncreasing our understanding of how these factors contribute to poorer outcomes among Nigerian women may uncover valuable insights and strategies in alleviating the TNBC burden in many countries of the world and help reduce the racial disparity in BC-related outcomes here in the United States. Importantly, this review also highlights collaborative global and local initiatives that converge expertise and resources to advance research on effective management of TNBC in diverse populations.

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Beyond triple-negative breast cancer and African ancestry: Tumor phenotypes among internationally diverse patient populations.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1101 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1101-1101

Author(s):

Evelyn Mawunyo Jiagge ◽

Aisha Jibril ◽

George Divine ◽

Kofi K. Gyan ◽

Jessica Miley Bensenhaver ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

African Ancestry ◽

West African ◽

Stem Cell Marker ◽

Breast Cancers ◽

East African ◽

Increased Risk ◽

West African Ancestry

1101 Background: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and HER2/ neu(triple negative breast cancer {TNBC}) are higher among African American (AA) compared to White American (WA) women. Several studies show higher TNBC frequency among selected populations of African patients. The colonial-era trans-Atlantic slave trade resulted in shared West African ancestry between contemporary AA and Ghanaian (Gh) populations. The extent to which TNBC susceptibility is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers such as Androgen Receptor (AR) and mammary stem cell marker ALDH1 is unknown. Methods: We used immunohistochemistry to assess ER, PR, HER2/ neu, AR and ALDH1 among WA (n = 153); AA (n = 76); Ethiopian (Eth)/East African (n = 90) and (Gh)/West African (n = 286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43; 49; 60; and 57 years for the Eth; Gh; AA; and WA patients, respectively. Frequency of TNBC was significantly higher for AA and Gh patients (54% and 41%, respectively) compared to WA and Eth patients (23% and 15%, respectively); p < 0.001. These associations were unchanged when limited to patients age 50 and younger (47% and 49% for AA and Gh, respectively; versus 18% and 16% for WA and Eth, respectively); p < 0.001. Frequency of ALDH1 positivity was also higher for tumors from AA and Gh patients (32% and 36%, respectively) compared to those from WA and Eth patients (23% and 17%, respectively); p = 0.007. Significant differences were observed for distribution of AR positivity, which was 71%; 55%; 42% and 50% for the WA; AA; Gh; and Eth cases, respectively (p = 0.008). Conclusions: We found a correlation between extent of African ancestry and risk of particular BC phenotypes. West African ancestry was associated with increased risk of TNBC and breast cancers that are positive for ALDH1. Future studies of hereditary TNBC susceptibility among women with African ancestry are warranted.

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Investigation of Triple-Negative Breast Cancer Risk Alleles in An International African-Enriched Cohort

10.21203/rs.3.rs-109841/v1 ◽

2020 ◽

Author(s):

Rachel Martini ◽

Yalei Chen ◽

Brittany Jenkins ◽

Isra Elhussin ◽

Esther Cheng ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Therapeutic Potential ◽

African Ancestry ◽

Case Series ◽

European Ancestry ◽

Risk Alleles

Abstract Large-scale efforts to identify breast cancer risk alleles have historically taken place among women on European ancestry, with recent efforts to validate these alleles or identify risk alleles applicable to women of African descent. We investigated the effect of previously reported breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case-control and nested case-series approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.4204, p = 0.005). We have shown that differential prevalence of the protective allele may reflect a polymorphic function of ANKLE1 in TNBC breast cancer outcomes. These AA specific risk alleles present opportunities for future studies of therapeutic potential that address race-specific differences in BC and TNBC risk and disease outcome.

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Abstract PL03-03: High-risk/triple-negative breast cancer and African ancestry

10.1158/1055-9965.disp-11-pl03-03 ◽

2011 ◽

Author(s):

Lisa A. Newman

Keyword(s):

Breast Cancer ◽

High Risk ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

African Ancestry

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African Ancestry and Triple-Negative Breast Cancer in the Women’s Health Initiative

The American Surgeon ◽

10.1177/0003134820949518 ◽

2020 ◽

pp. 000313482094951

Author(s):

Veronica C. Jones ◽

Rowan T. Chlebowski ◽

Kathy Pan ◽

Laura Kruper ◽

Joanne Mortimer ◽

...

Keyword(s):

Breast Cancer ◽

Women’S Health ◽

Women's Health ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

African Ancestry ◽

Women's Health Initiative ◽

Women’S Health Initiative ◽

Health Initiative ◽

The Women’S Health Initiative

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Triple Negative Breast Cancer in Pregnancy and Postpartum: Two Case Reports in Hispanic Women

Case Reports in Obstetrics and Gynecology ◽

10.1155/2015/856931 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Ruchi Upadhyay ◽

Qurat-Ul-Ain Butt ◽

Abraham Hamaoui ◽

Cassandra Henderson ◽

Sydney McCalla ◽

...

Keyword(s):

Breast Cancer ◽

Invasive Ductal Carcinoma ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Ductal Carcinoma ◽

Hispanic Women ◽

African Ancestry ◽

Radical Mastectomy ◽

Unique Challenge ◽

Pregnancy And Postpartum

Objective. Despite studies suggesting that triple negative breast cancer is more often seen in women of African ancestry, we report here two cases of pregnancy associated triple negative breast cancer in Hispanic women.Cases. Case one is a 37-year-old female para 2-0-0-2, who presented with a left breast mass, at 19 weeks of gestation, the biopsy of which reported an invasive ductal carcinoma, found to be triple receptor negative. The patient underwent chemotherapy during the pregnancy and was delivered with a cesarean at 37 weeks for obstetric indication. After delivery, the patient completed her chemotherapy that was followed by radical mastectomy and radiotherapy. Case two is a 28-year-old female para 6-0-1-5, who presented while breast-feeding with signs and symptoms of mastitis, and an engorged and tender right breast, five months postpartum. However, the sonogram revealed a fluid filled cavity. Aspiration and cytology did not reflect an infection and were negative for malignancy. High suspicion and lack of improvement led to biopsy that identified an invasive ductal carcinoma, found to be triple negative. The patient underwent chemotherapy followed by modified radical mastectomy.Conclusions. Triple negative breast cancer, during pregnancy or postpartum, poses a unique challenge and requires a multidisciplinary team to optimize treatment for these women.

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