Table 2.
Selected adjuvant studies assessing the role of TILs in early HER2-positive breast cancer
| Trial(s) | Sample size in sTIL analysis (HER2-positive) | Eligibility and regimen | sTIL cut-off | Positive association with long-term outcomes |
|---|---|---|---|---|
| BIG 02-98 a79 | 297 | Node + A-CMF, AC-CMF, A-T-CMF, AT-CMFa | Continuous variable (10% increase), or ≥50% LPBC | ✓ Increase in TILs was associated with decreased risk of recurrence and decreased risk of death |
| NSABP B-3139 | 1581 | Node + or >2 cm if ER+/PR+ or >1 cm if ER-/PR-AC→T ± H | Semicontinuous variable, or ≥50% LPBC | ✓ Disease-free survival |
| FinHER24 | 209 | Node + or ≥2 cm and PR− FEC + V or D ± H |
Continuous variable (10% increase) | ✓ Increase in TILs was associated with decreased risk of recurrence |
| ShortHER51 | 866 | Node+ or node– with one of the following: ≥2 cm tumor, G3, LVI, <35 years of age, ER/PR <10% EC → T + H to complete a year versus docetaxel + H 9 weeks → FEC 9 weeks | Continuous variable (1% increase) or ≥20% | ✓ Distant disease-free survival |
| N983140 | 945 | AC→T ± H (Arm A = no H, arm C = H) | Continuous variable (10% increase) or ≥60% | ✓ Recurrence-free survival in arm A |
| APHINITY56 | 4313 | Stage I-III Chemotherapy + H ± P | Continuous variable and by quartiles | ✓b |
Green: positive association, red: negative association, gray: not studied/not applicable.
AC→T, doxorubicin, cyclophosphamide followed by paclitaxel; cape, capecitabine; CMF, cyclophosphamide, methrotexate, 5-fluorouracil; EC→T, epirubicin + cyclophosphamide → docetaxel; ED, epirubicin and docetaxel; ER, estrogen receptor; FEC, fluorouracil, epirubicin, cyclophosphamide; H, trastuzumab; HER2, human epidermal growth factor receptor 2; HL, trastuzumab + lapatinib; HR, hormone receptor; L, lapatinib; LPBC, lymphocyte-predominant breast cancer; LVI, lymphovascular invasion; pCR, pathologic complete response; PR, progesterone receptor; sTIL, stromal tumor-infiltrating lymphocyte; V or D, docetaxel or vinorelbine.
Trial designed before the routine use of trastuzumab, the interaction between increasing sTIL and benefit with anthracycline-only chemotherapy (P = 0.018).
‘Better outcomes’, details unavailable.