Hiroaki Inoue1, Rie Horii2,3, Yoshinori Ito4, Takuji Iwase5, Shinji Ohno6, Futoshi Akiyama1,7. 1. Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. 2. Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. rhorii-pathology@jfcr.or.jp. 3. Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. rhorii-pathology@jfcr.or.jp. 4. Department of Breast Medical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 5. Department of Breast Surgical Oncology, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 6. Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 7. Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Abstract
BACKGROUND: Immune responses play an important role in interrupting the progression of cancer cells. Tumor-infiltrating lymphocytes (TILs) are basic components of the immune system. In triple negative breast cancer, increased number of TILs is associated with excellent prognosis and response of chemotherapy. Here, we investigated whether TILs affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: The study included 97 patients with stage I-III HER2-positive breast cancer. All patients were preoperatively treated with an anthracycline-based combination regimen, followed by taxane with trastuzumab from 2009 to 2013. Pathological complete response (pCR) was defined as the disappearance of invasive cancer cells regardless of the presence of in situ components. TILs were evaluated using pre-therapeutic needle biopsy specimens. We assessed the percentage of the breast stroma with TILs over the total intratumoral stroma and classified the specimens in three grades: TILs1+ < 30%, TILs2+ 30-50%, and TILs3+ > 50%. RESULTS: Overall, 80.4% of the specimens were TILs1+, 15.5% were TILs2+ and 4.1% were TILs3+. The pCR rate was 44.9% (35/78) in the TILs1+ cases, 80.0% (12/15) in the TILs2+ cases and 75.0% (3/4) in the TILs3+ cases. TILs were significantly associated with pCR (P = 0.0228). Multivariate analysis using TILs, hormone receptor (HR), nuclear grade (NG) and age indicated that TILs (OR 4.32, 95% CI 1.04-23.33, P = 0.0436) and HR (OR 8.76, 95% CI 3.30-25.44, P < 0.0001) were independent predictors for pCR. CONCLUSION: TILs are associated with the efficacy of trastuzumab-based treatment in HER2-positive breast cancer.
BACKGROUND: Immune responses play an important role in interrupting the progression of cancer cells. Tumor-infiltrating lymphocytes (TILs) are basic components of the immune system. In triple negative breast cancer, increased number of TILs is associated with excellent prognosis and response of chemotherapy. Here, we investigated whether TILs affect the efficacy of trastuzumab-based treatment in humanepidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS: The study included 97 patients with stage I-III HER2-positive breast cancer. All patients were preoperatively treated with an anthracycline-based combination regimen, followed by taxane with trastuzumab from 2009 to 2013. Pathological complete response (pCR) was defined as the disappearance of invasive cancer cells regardless of the presence of in situ components. TILs were evaluated using pre-therapeutic needle biopsy specimens. We assessed the percentage of the breast stroma with TILs over the total intratumoral stroma and classified the specimens in three grades: TILs1+ < 30%, TILs2+ 30-50%, and TILs3+ > 50%. RESULTS: Overall, 80.4% of the specimens were TILs1+, 15.5% were TILs2+ and 4.1% were TILs3+. The pCR rate was 44.9% (35/78) in the TILs1+ cases, 80.0% (12/15) in the TILs2+ cases and 75.0% (3/4) in the TILs3+ cases. TILs were significantly associated with pCR (P = 0.0228). Multivariate analysis using TILs, hormone receptor (HR), nuclear grade (NG) and age indicated that TILs (OR 4.32, 95% CI 1.04-23.33, P = 0.0436) and HR (OR 8.76, 95% CI 3.30-25.44, P < 0.0001) were independent predictors for pCR. CONCLUSION: TILs are associated with the efficacy of trastuzumab-based treatment in HER2-positive breast cancer.
Entities:
Keywords:
Breast cancer; Human epidermal growth factor receptor 2; Neoadjuvant chemotherapy; Pathology; Tumor-infiltrating lymphocytes
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