PMID- 28937963 OWN - NLM STAT- MEDLINE DCOM- 20180723 LR - 20220317 IS - 1868-1891 (Electronic) IS - 1868-1883 (Linking) VI - 32 IP - 2 DP - 2017 Sep 22 TI - Ki67 and lymphocytes in the pretherapeutic core biopsy of primary invasive breast cancer: positive markers of therapy response prediction and superior survival. LID - /j/hmbci.2017.32.issue-2/hmbci-2017-0022/hmbci-2017-0022.xml [pii] LID - 10.1515/hmbci-2017-0022 [doi] AB - Background Core needle biopsy plays a crucial role as diagnostic tool for BC. Both Ki67 and likely tumor-infiltrating lymphocytes (TILs) in the near future are determining the kind of systemic therapy. The role of TILs in BC is still an issue for clinical research, albeit preliminary results of neoadjuvant and adjuvant clinical studies already now highlight the crucial impact of TILs on therapy response and survival. Methods Evaluation of related publications (pubmed) and meeting abstracts (ASCO, SABCS). Results The monoclonal antibody Ki67 recognizing a nuclear antigene in proliferating cells is a positive marker of therapy response and superior survival. Endocrine responsive tumors of low proliferation (Ki67 < 14%/11%) respond to tamoxifen, in contrast postmenopausal tumors with higher proliferation respond better to aromatase-inhibitors. Pathological complete response (pCR)-rates increase in tumors with higher proliferation (Ki67 > 19%) vs. tumors with lower proliferation after neoadjuvant chemotherapy (NAC). pCR-rates of up to 60% can be seen in TNBC and HR-, HER2+BC, lower pCR-rates, however, in HR+, HER2- BC. Increased stromal TILs are found in 30% of TNBC and in 19% of HR-, HER2+BC. The percentage of TILs is a significant independent parameter for pCR after NAC. Lymphocyte-predominant BC (LPBC) respond with higher pCR-rates than non-LPBC or tumors without any TILs. Increased TILs in TN and HR-, HER2+ subtypes predict benefit from addition of carboplatin to NAC. TILs are also associated with improved DFS and OS among patients with TNBC and HR-, HER2+ BC. Conversly and interestingly increased TILs in patients with HR+, HER2-(luminal) BC are associated with a 10% higher risk of death per 10% increase of TILs. Interactions between immune system and cancer are complex. The cancer-immunity cycle characterizes these interactions. BC subtypes with higher number of mutations such as TNBC and HR-, HER2+BC are considered to provide a raising number of tumor-associated antigens, thereby capable to build up a higher endogenous immune response. TILs may serve as surrogate marker of both an existing endogenous immune response and the probability to respond to cancer immune therapies. As cancer co-opt immune checkpoint-pathways as a major mechanism of immune resistance, in particular, against cytotoxic T-cells, blockades of checkpoint-pathways by antibodies are one of the goals of the current cancer immunotherapy studies. Therapy studies with antigene-based strategies (vaccines) and antibodies against the immune checkpoints PD-1 and CTLA-4 and their inhibitory pathways in order to enhance cytotoxic T-cell activities against cancer cells with or without chemotherapy are underway. Conclusions It can be suggested that the use of multigene expression testing will increase in order to select more clearly primary HR+, HER2- BC patients with intermediate recurrence risk who likely may benefit from chemotherapy. Furthermore Ki67 and the multigene expression test Oncotype DX can act as dynamic markers to avoid cytostatic overtreatment and endocrine undertreatment. A data-derived optimal Ki67 cut point for pCR and DFS as well as OS is currently not feasible. The integration of stromal TILs into the immunohisto-pathological report after their evaluation has been standardized is likely helpful to determine patients who profit by additional carboplatin chemotherapy. Oncologists need an enlarged information about the tumor-microenvironment in future. The preliminary results of current BC immunotherapy studies are encouraging. FAU - Schlotter, Claus M AU - Schlotter CM AD - Department of Obstetrics and Gynecology, Klinikum-Mittelbaden, Breast Center, D-76532 Baden-Baden, Balger-Str. 50, Germany, Phone: +4917620123472. FAU - Tietze, Lothar AU - Tietze L AD - Institute of Pathology, Ortenau Klinikum Lahr-Ettenheim, Lahr, Germany. FAU - Vogt, Ulf AU - Vogt U AD - European Laboratory Association, Ibbenbueren, Germany. FAU - Heinsen, Carlos Villena AU - Heinsen CV AD - Department of Obstetrics and Gynecology, Luzerner Kantonsspital Sursee, Sursee, Switzerland. FAU - Hahn, Antje AU - Hahn A AD - Department of Obstetrics and Gynecology, Breast Center, Klinikum-Mittelbaden, Baden-Baden, Germany. LA - eng PT - Evaluation Study PT - Journal Article PT - Review DEP - 20170922 PL - Germany TA - Horm Mol Biol Clin Investig JT - Hormone molecular biology and clinical investigation JID - 101538885 RN - 0 (Ki-67 Antigen) SB - IM MH - Breast Neoplasms/metabolism/*pathology/therapy MH - Female MH - Humans MH - Ki-67 Antigen/*blood MH - Lymphocytes/*pathology MH - Neoplasm Invasiveness MH - Survival Analysis OTO - NOTNLM OT - anti-tumor immune response OT - endocrine therapy OT - lymphocyte tumor infiltration OT - neoadjuvant chemotherapy OT - pretherapeutic core biopsy OT - primary breast cancer OT - proliferation marker Ki67 OT - therapy response prediction EDAT- 2017/09/25 06:00 MHDA- 2018/07/24 06:00 CRDT- 2017/09/23 06:00 PHST- 2017/04/25 00:00 [received] PHST- 2017/07/22 00:00 [accepted] PHST- 2017/09/25 06:00 [pubmed] PHST- 2018/07/24 06:00 [medline] PHST- 2017/09/23 06:00 [entrez] AID - /j/hmbci.ahead-of-print/hmbci-2017-0022/hmbci-2017-0022.xml [pii] AID - 10.1515/hmbci-2017-0022 [doi] PST - epublish SO - Horm Mol Biol Clin Investig. 2017 Sep 22;32(2):/j/hmbci.2017.32.issue-2/hmbci-2017-0022/hmbci-2017-0022.xml. doi: 10.1515/hmbci-2017-0022.