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TILs Indicate Outcome in Young Patients Not Receiving Systemic Adjuvant Treatment for TNBC

Tumour infiltrating lymphocyte levels may inform treatment decisions in women younger than 40 years with triple negative breast cancer
20 Sep 2020
Breast cancer;  Pathology/Molecular biology

Young women who did not receive systemic adjuvant treatment for triple negative breast cancer (TNBC), but who were found to have increased levels of tumour infiltrating lymphocytes (TILs), demonstrated improved survival outcomes and a lower risk of tumour recurrence compared with similar patients having lower TIL levels, Vincent M.T. De Jong, MD of the Molecular Pathology, Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital in Amsterdam, Netherlands reported at the ESMO Virtual Congress 2020.

De Jong and colleagues in the PARADIGM study group investigated the prognostic value of stromal TILs to resolve whether all women younger than 40 years with node negative TNBC benefit from (neo)adjuvant chemotherapy.

He pointed out that, to date, there is a paucity of data in young patients to guide this decision.

For study inclusion, the investigators reviewed the Netherlands Cancer Registry for the years from 1989 to 2000 to identify all women <40 years who were diagnosed with TanyN0M0 breast cancer but did not receive systemic adjuvant treatment.

Following reassessment of the oestrogen receptor (ER), progesterone receptor (PgR), and HER2 status, TILs were scored according to an established standard for the triple negative subset; defined as having less than 10% ER or PgR expression and were also HER2 negative.

Using covariates that included TIL score, T stage, tumour grade, and the local treatment administered, the investigators performed multivariable Cox regression to determine overall survival (OS). For distant metastasis-free survival (DMFS) the investigators performed a competing-risk model with the occurrence of a second primary tumour as the competing risk. All patients without an event were right censored at 15 years follow-up.

This study comprised 481 patients with TNBC with a median age of 35 (range, 22 to 39) years.

Eighty-six percent of these women had grade 3 tumours and 49% had pT1C tumours.

The median TIL score was 25% (interquartile range 5 – 70).

During follow-up, 87 (18%) patients developed a second primary tumour. The analysis revealed 117 DMFS events in 24% of the patients, which included 85 metastases and 32 deaths. An additional 138 (39%) deaths overall occurred.

Survival rates were improved in patients with higher TIL levels

In all, 127 patients had TIL levels within a range of ≥30%, but <75%; these patients demonstrated 10-year OS of 80% (95% confidence interval [CI] 73 - 87) and 15-year OS of 76% (95% CI 69 – 84). The DMFS incidence rates at 10 and 15 years were 15% (95% CI 12 - 18) and 16% (95% CI 12 - 19), respectively. While the incidence rate of the competing risk, second primary tumour, was 20% (95% CI 17 - 23) and 22% (95% CI 19 - 26), respectively.

In comparison, 107 patients having higher TIL levels (≥75%) demonstrated prolonged OS with 10-year OS of 95% (95% CI 91 – 100) and 15-year OS of 93% (95% CI 89 – 99). The DMFS incidences at 10 and 15 years were also improved to 2% (95% CI 0 – 3) and 2% (95% CI 0 – 3), respectively. While the incidence rate of the competing risk, second primary tumour, stayed comparable at 18% (95% CI 14 - 21) and 23% (95% CI 19 - 27), respectively.

Every increase of a 10% increment of TILs reduced the risk of death (adjusted hazard ratio [HR] 0.81; 95% CI 0.79 - 0.88).


Stromal TILs can distinguish high-risk and very low-risk in a cohort of young, node-negative, triple-negative breast cancer patients who did not receive systemic therapy. High-risk patients, with <30% stromal TILs, have a 15-year OS of 59%; very low-risk patients, with ≥75% stromal TILs have a 15-year OS of 93%.

© Vincent M.T. De Jong. 


Based on these data the authors were able to conclude that TIL status may provide important prognostic information in patients less than 40 years of age with systemically untreated node negative TNBC.

They suggested that subsequent investigations are warranted to determine whether systemic adjuvant therapy can be de-escalated in this subgroup of young TNBC patients with higher TIL levels.

This study was funded by ZonMw A Sister's Hope Vrienden UMC Utrecht. 


159O - De Jong VMT, Wang Y, Opdam M, et al. Prognostic value of tumor infiltrating lymphocytes in young triple negative breast cancer patients who did not receive adjuvant systemic treatment; by the PARADIGM study group. ESMO Virtual Congress 2020.

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