Triple-Negative Breast Cancer (TNBC) is a heterogeneous and aggressive disease which, compared to other breast cancer subtypes, has faster growing, less differentiated and higher histologic grade tumors that tend to be larger at diagnosis1,3,4.
TNBC is defined by the lack of expression of estrogen receptor (ER) and progesterone receptor (PR) and absence of HER2 overexpression and/or gene amplification, key drivers that are characteristic for other breast cancer subtypes3. They represent a heterogeneous breast cancer subtype with poor prognosis and patients are typically diagnosed at younger age compared to other breast cancer subtypes1,3,4,5.
Who is most at risk to develop breast cancer?
The major risk factors for developing breast cancer are female gender, age ≥65 years, having lobular carcinoma in situ or atypical hyperplasia, and having BRCA1/2 mutations1,2,4,6. In addition, a family history of breast cancer, breasts with high density on mammography, high endogenous, postmenopausal hormone levels and a history of high-dose radiation to the chest may also increase the risk of developing breast cancer4.
Compared with other breast cancer subtypes, TNBC usually affects younger women more frequently, is more prevalent in black women, and shows a higher prevalence of germline BRCA mutations3.
How many TNBC patients are there in Belgium?
According to data from the Belgian Cancer Registry, approximately 1.216 patients will be diagnosed each year with TNBC, representing 9-11% of all new breast cancer diagnosis7.
Furthermore, a significant proportion of patients having received past diagnosis of breast cancer will experience during their lifetime a relapse of disease with a new and different histologic profile, a dismal diagnosis suggestive of a more aggressive disease, with high metastatic potential and poor response to therapy8.
What is the prognosis?
Survival rates for breast cancer are generally relatively high in developed countries with a 5-year survival of 85-90% in Belgium and other Western countries10. The median overall survival for all metastatic breast cancer subtypes from metastatic diagnosis is 32 months. Median overall survival is longest for patients with HER2+ breast cancer, followed by HR+ breast cancer, while TNBC patients have the shortest survival (54 months vs 36 months vs 17 months, respectively)10.
Stage at diagnosis is one of the most important factors affecting prognosis. Five-year relative survival rates for breast cancer are: 99% for localized disease, 86% for regional disease, and 30% for patients diagnosed with metastatic disease12,13. Breast cancer survival also varies by tumor subtype. Five-year relative survival rates are: 92% for HR+/HER2-, 89% for HR+/HER2+, 83% for HR-/HER2+, 77% for HR-/HER2- (TNBC)12,13. For TNBC specifically, 5-year relative survival rates are 91% for localized disease, 66% for regional disease, and only 12% for patients diagnosed with metastatic disease12,13.
What is the medical need in mTNBC?
Until recently, treatment for metastatic TNBC patients has relied almost exclusively on non-selective cytotoxic agents, with modest success as overall survival by year of metastatic diagnosis has not improved over time from 2008 till 201611. Furthermore, treatment with conventional chemotherapy, has a limited median survival of 12 to 18 months and an estimated 5-year overall survival of 12%12,13, underscoring the very high unmet medical need of these patients lacking innovative therapeutic options for the treatment of these heterogeneous and aggressive tumors.
Recent advances in the use of PARP inhibitors and immune checkpoint blockade offer more targeted solutions for some of these patients in the metastatic setting. However, a prominent unmet medical need remains for patients relapsing or not eligible to receive immunotherapy such as anti PD-(L)1 agents or targeted therapies, such as PARP inhibitors3,5.
Lee A, Djamgoz MBA. Triple negative breast cancer : Emerging therapeutic modalities and novel combination therapies. Cancer Treat Rev. 2018;62:110-22
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative and HER2-negative invasive breast cancer, the so-called triple negative
phenotype: a population-based study from the California cancer registry. 2007;109(9):172-8.
Linda Lindstrom et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor 2 are unstable throughout tumor progression. J of Clin Oncol
Sung et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA CANCER J CLIN 2021;71:209-249
Seah DSE et al. Use and Duration of Chemotherapy in patients with metastatic breast cancer according to tumor subtype and line of therapy. J Natl Compr Canc Netw. 2014;12(1):71-80.
T Grinda et al. Evolution of overall survival and receipt of new therapies by subtype among 20446 metastatic breast cancer patients in the 2008-2017 ESME cohort. ESMO Open Cancer Horizons 2021