@article{LoebLinsmeierHerbertetal.2023,
  author    = {L{\"o}b, Sanja and Linsmeier, Eva and Herbert, Saskia-Laureen and Schlaiß, Tanja and Kiesel, Matthias and Wischhusen, J{\"o}rg and Salmen, Jessica and Kranke, Peter and Quenzer, Anne and Kurz, Florian and Weiss, Claire and Gerhard-Hartmann, Elena and W{\"o}ckel, Achim and Diessner, Joachim},
  title     = {Prognostic effect of HER2 evolution from primary breast cancer to breast cancer metastases},
  series = {Journal of Cancer Research and Clinical Oncology},
  volume    = {149},
  journal   = {Journal of Cancer Research and Clinical Oncology},
  number    = {8},
  doi       = {10.1007/s00432-022-04486-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324068},
  pages     = {5417-5428},
  year      = {2023},
  abstract  = {Purpose Therapeutic options for breast cancer (BC) treatment are constantly evolving. The Human Epidermal Growth Factor 2 (HER2)-low BC entity is a new subgroup, representing about 55\% of all BC patients. New antibody-drug conjugates demonstrated promising results for this BC subgroup. Currently, there is limited information about the conversion of HER2 subtypes between primary tumor and recurrent disease. Methods This retrospective study included women with BC at the University Medical Centre Wuerzburg from 1998 to 2021. Data were retrieved from patients' records. HER2 evolution from primary diagnosis to the first relapse and the development of secondary metastases was investigated. Results In the HR-positive subgroup without HER2 overexpression, HER2-low expression in primary BC was 56.7 vs. 14.6\% in the triple-negative subgroup (p < 0.000). In the cohort of the first relapse, HER2-low represented 64.1\% of HR-positive vs. 48.2\% of the triple-negative cohort (p = 0.03). In patients with secondary metastases, HER2-low was 75.6\% vs. 50\% in the triple negative subgroup (p = 0.10). The subgroup of HER2-positive breast cancer patients numerically increased in the course of disease; the HER2-negative overall cohort decreased. A loss of HER2 expression from primary BC to the first relapse correlated with a better OS (p = 0.018). No clinicopathological or therapeutic features could be identified as potential risk factors for HER2 conversion. Conclusion HER2 expression is rising during the progression of BC disease. In view of upcoming therapeutical options, the re-analysis of newly developed metastasis will become increasingly important.},
  language  = {en}
}
@article{DiessnerBruttelBeckeretal.2013,
  author    = {Diessner, Joachim and Bruttel, Valentin and Becker, Kathrin and Pawlik, Miriam and Stein, Roland and H{\"a}usler, Sebastian and Dietl, Johannes and Wischhusen, J{\"o}rg and H{\"o}nig, Arnd},
  title     = {Targeting breast cancer stem cells with HER2-specific antibodies and natural killer cells},
  series = {American Journal of Cancer Research},
  volume    = {3},
  journal   = {American Journal of Cancer Research},
  number    = {2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128633},
  pages     = {221-220},
  year      = {2013},
  abstract  = {Breast cancer is the most common cancer among women worldwide. Every year, nearly 1.4 million new cases of breast cancer are diagnosed, and about 450.000 women die of the disease. Approximately 15-25\% of breast cancer cases exhibit increased quantities of the trans-membrane receptor tyrosine kinase human epidermal growth factor receptor 2 (HER2) on the tumor cell surface. Previous studies showed that blockade of this HER2 proto-oncogene with the antibody trastuzumab substantially improved the overall survival of patients with this aggressive type of breast cancer. Recruitment of natural killer (NK) cells and subsequent induction of antibody-dependent cell-mediated cytotoxicity (ADCC) contributed to this beneficial effect. We hypothesized that antibody binding to HER2-positive breast cancer cells and thus ADCC might be further improved by synergistically applying two different HER2-specific antibodies, trastuzumab and pertuzumab. We found that tumor cell killing via ADCC was increased when the combination of trastuzumab, pertuzumab, and NK cells was applied to HER2-positive breast cancer cells, as compared to the extent of ADCC induced by a single antibody. Furthermore, a subset of \(CD44^{high}CD24^{low}HER2^{low}\) cells, which possessed characteristics of cancer stem cells, could be targeted more efficiently by the combination of two HER2-specific antibodies compared to the efficiency of one antibody. These in vitro results demonstrated the immunotherapeutic benefit achieved by the combined application of trastuzumab and pertuzumab. These findings are consistent with the positive results of the clinical studies, CLEOPATRA and NEOSPHERE, conducted with patients that had HER2-positive breast cancer. Compared to a single antibody treatment, the combined application of trastuzumab and pertuzumab showed a stronger ADCC effect and improved the targeting of breast cancer stem cells.},
  language  = {en}
}