Abstract PS6-49: Intratumoral cytotoxic t-lymphocyte numbers and chemokine predict long-term survival of triple-negative breast cancer independently of tumor mutational burden

10519 Objective. Triple-negative breast cancer is defined as a subtype of invasive breast cancer which lacks estrogen and progesterone receptor expression as well as HER2/neu expression and is highly similar to the basal-like subtype defined by gene expression profiling. Method. 1,143 patients treated at MD Anderson Cancer Center in neoadjuvant trials were included in a retrospective comparative analysis between triple-negative tumors and non-triple-negative tumors for response to neoadjuvant chemotherapy as well as long- term survival. Results. 827/1,143 (72%) patients had received taxanes, either as a single-agent (n=60) or in combination with anthracycline (n=767), whereas the remainder patients received an anthracycline-only chemotherapy. Overall 258/1,143 (23%) tumors were triple- negative. Complete pathological response (pCR) was achieved in 63/257 (25%) patients with triple-negative tumors compared to 99/888 (11%) in patients with non-triple-negative tumors (odds ratio [OR] 1.14, 95%CI: 1.09–1.20, p=.0082). Triple-negative status correlated significantly with high nuclear grade (p<.0001), whereas no significant correlation with any established clinicopathologic parameter was observed. However, 5-year overall survival (5yrOS) was 66% in the triple-negative group compared to 83% in the non-triple-negative control group (OR 2.1, 95%CI: 1.6–2.8, p<.0001). In multivariate analyses, triple-negative status (hazard ratio [HR] 2.0, 95%CI: 1.4–2.8, p<.0001), high nuclear grade, increased tumor size (HR 1.5, 95%CI: 1.3–1.8, p<.0001), positive nodal status (HR 1.4, 95%CI: 1.2–1.7, p=.0002) and high nuclear grade (HR 1.7, 95%CI: 1.1- 2.4, p=.0089) were significantly associated with decreased 5yrOS. When survival was analyzed according to both response rate and triple negative status, achievement of pCR was a stronger predictor of survival compared to triple-negative status. Conclusion. Triple- negative expression status among patients with breast cancer constitutes an independent unfavorable prognostic factor with regards to overall survival unless achieving pCR after neoadjuvant chemotherapy. No significant financial relationships to disclose.

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Long-term survival in a patient with bilateral metachronous triple negative breast cancer: A case report and literature review

Archives of International Surgery ◽

10.4103/ais.ais_19_19 ◽

2018 ◽

Vol 8 (4) ◽

pp. 176

Author(s):

IsmailHadi Zubairu ◽

SundayAdeyemi Adewuyi

Keyword(s):

Breast Cancer ◽

Case Report ◽

Literature Review ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Term Survival ◽

Long Term Survival

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Cytotoxic T-lymphocyte infiltration and chemokine predict long-term patient survival independently of tumor mutational burden in triple-negative breast cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211006680 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110066

Author(s):

Eriko Katsuta ◽

Li Yan ◽

Mateusz Opyrchal ◽

Pawel Kalinski ◽

Kazuaki Takabe

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Patient Survival ◽

Cytotoxic T Lymphocyte ◽

Breast Cancer Patients ◽

Mutational Burden ◽

Cancer Immunity ◽

Anti Cancer ◽

Tumor Mutational Burden ◽

Patient Prognosis

Background: Cytotoxic T-lymphocyte (CTL) infiltration into tumor is a positive prognostic factor in breast cancer. High tumor mutational burden (TMB) is also considered as a predictor of tumor immunogenicity and response to immunotherapy. However, it is unclear whether the infiltration of functional CTL simply reflects the TMB or represents an independent prognostic value. Methods: Utilizing The Cancer Genome Atlas (TCGA) breast cancer cohort, we established the Functional Hotness Score (FHS). The associations of FHS and breast cancer patient prognosis as well as distinct immunity markers were analyzed in a total of 3011 breast cancer patients using TCGA, METABRIC and metastatic breast cancer (MBC) cohort GSE110590. Results: We established FHS, based on CD8A, GZMB and CXCL10 gene expression levels of bulk tumors, which delivered the best prognostic value among some gene combinations. Breast cancer patients with the high-FHS tumors showed significantly better survival. FHS was lower in the MBCs. Triple-negative breast cancer (TNBC) showed the highest FHS among subtypes. FHS predicted patient survival in hormone receptor (HR)-negative, especially in TNBC, but not in HR-positive breast cancer. FHS predicted patient prognosis independently in TNBC. The high-FHS TNBCs showed not only higher CD8+ T cell infiltration, but also enhanced broader type-1 anti-cancer immunity. The patients with the high-FHS tumors showed better prognosis not only in high-TMB tumors but also in low-TMB TNBCs. The combination of high-TMB with high-FHS identified a unique subset of patients who do not recur over time in TNBC. Conclusion: TNBCs with high FHS based on the expression levels of CD8A, GZMB and CXCL10 showed improved prognosis with enhanced anti-cancer immunity regardless of TMB. FHS constitutes an independent prognostic marker of survival, particularly robustly when combined with TMB in TNBC.

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