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3. current projects
Current clinical studies
WSG ADAPT-TN-III (2024-2027)
This clinical trial of the West German Study Group (WSG) aims to find a well-tolerated and highly effective de-escalating therapy for early triple negative breast cancer. It is investigating whether the combination therapy of sacituzumab govitecan + pembrolizumab achieves a higher rate of pathological complete remissions than therapy with sacituzumab govitecan alone. The aim is to avoid prolonged and more toxic treatment. 350 patients will be included in this study and will undergo a central histologic evaluation. The Clinical Trials in Breast Cancer working group will act as the central reference pathology and tissue bank for the ADAPT-TN-II trial.
WSG ADAPT-HER2-IV (2024-2026)
This clinical trial of the West German Study Group (WSG) is dedicated to the treatment of HER2-positive early breast cancer. It compares neoadjuvant treatment with trastuzumab-deruxtecan (T-DXd) for 12 or 18 weeks in two experimental study arms versus standard-of-care therapy (e.g. neoadjuvant therapy with paclitaxel + trastuzumab + pertuzumab). Primary endpoints are pCR rate after neoadjuvant therapy and 3-year distant-disease-free survival (dDFS). This is a prospective, multicentre, randomized, open phase II study to optimize therapy. More than 400 breast cancer cases will undergo a central histological assessment as part of this study. The Clinical Trials in Breast Cancer working group will act as the central reference pathology and tissue bank for the ADAPT-HER2-IV trial.
WSG ADAPTcycle (2020-2023)
This clinical trial of the West German Study Group (WSG) implements an adjuvant dynamic marker-adapted personalized therapy strategy (ADAPT) and compares endocrine therapy plus ribociclib (CDK4/6 inhibitor) with endocrine therapy plus chemotherapy for hormone receptor-positive, HER2-negative breast cancer with intermediate risk of recurrence in the early stage. This is a prospective, multicenter, randomized, open phase III trial. Over 5500 breast carcinomas will undergo initial screening and over 1600 patients will be randomized. The Clinical Trials in Breast Cancer working group will act as the central reference pathology and tissue bank for ADAPTcycle.
Current basic scientific studies
Investigations into the molecular phenotype of osteoclast-like giant cells in breast cancer (2024-2025)
Breast carcinomas with osteoclast-like giant cells are a rare morphologic variant of invasive breast carcinoma. The osteoclast-like giant cells (OGC cells) are not actual tumor cells, but form from macrophages in the tumor stroma. This transformation is probably induced by paracrine signals from the carcinoma cells. In this project, the molecular phenotype of such OGC cells will be investigated in more detail. In particular, OGC cells in the tumor stroma of breast carcinomas are compared with multinucleated giant cells that form in the context of inflammatory processes (e.g. in tuberculosis and sarcoidosis).
GATA3 in collagenous spherulosis and adenoid cystic carcinoma (2023-2024)
Collagenous spherulosis (CS) of the breast is a benign lesion of unknown etiology. In KS, there is a deposition of acellular material surrounded by a layer of myoepithelial cells. Luminal differentiated epithelial cells are inserted between these myoepithelial cells. Mammary gland lobules are usually affected. KS is basically harmless, but has morphological similarities with adenoid cystic carcinoma (ACC) of the breast. AZK belongs to the spectrum of triple-negative (non-luminal) neoplasms of the breast and is frequently associated with rearrangement of the MYB gene. The differential diagnosis of a KS from an AZK using immunohistochemical staining can pose difficulties and require the use of extensive marker panels. GATA3 is a transcription factor that is expressed in luminal differentiated mammary epithelia. The current study investigates the extent to which GATA3 can be helpful in the differential diagnosis of a KS from an AZK.
Colon metastasis of lobular breast carcinoma (2022-2023)
In advanced stages, lobular breast cancer is associated with frequent metastasis to the abdominal cavity and especially to the colon. In most cases, there is no circumscribed tumor in the colon but changes that endoscopically mimic the appearance of colitis. As part of this project, a case collection of metastases of lobular breast carcinomas in the colon will be created. On the basis of this case collection, a detailed morphological and molecular pathological examination of the histologic changes in the intestine caused by metastatic lobular breast carcinoma will be performed.
Determinants of endocrine resistance (Endores) (2017-2023)
Endocrine therapy aims to block the estrogen receptor signaling pathway and is a highly effective treatment for breast cancer. Primary and acquired resistance can render endocrine therapy ineffective. This molecular pathology study is based on tissue samples from patients with breast cancer who underwent short-term endocrine therapy prior to tumor resection (WSG ADAPT study). Based on the proliferative activity of tumor cells in pre- and post-therapeutic tissue samples, individual patients or tumors can be classified as endocrine-responsive or endocrine-resistant. The study will define molecular changes associated with endocrine resistance. For this purpose, large cohorts of endocrine-responsive and endocrine-resistant tumors will be subjected to a detailed, comparative molecular analysis. This study is supported by third-party funding from German Cancer Aid.
Molecular pathology of lobular breast cancer
Lobular breast carcinoma is the most common specific histologic subtype of breast carcinoma. Inactivation of the cell adhesion molecule E-cadherin is the central molecular alteration in these tumors. These studies are investigating the extent to which the loss of E-cadherin is associated with specific secondary molecular changes and influences growth patterns and proliferative activity.
Molecular pathology of microglandular adenosis (MGA)
Microglandular adenosis of the breast (MGA) is an unusual, lump-forming disease of the mammary gland that is associated with an increased risk of carcinoma. Contrary to previous assumptions, MGA is not a reactive tissue remodeling but a clonal neoplasia. In this molecular pathology study, we are investigating the molecular pathological changes in MGA. Of particular interest is the pathognomonic loss of luminal differentiation markers in the epithelial cells of MGA.
3. current projects
Current clinical trials
WSG ADAPT-TN-III (2024-2027)
This clinical trial of the West German Study Group (WSG) aims to find a well-tolerated and highly effective de-escalating therapy for early triple negative breast cancer. This trial investigates whether the combination therapy of sacituzumab govitecan + pembrolizumab achieves a higher rate of pathological complete remission than therapy with sacituzumab govitecan alone. The aim is to avoid prolonged and more toxic treatment. 350 patients will be included in this study and will undergo a central histologic evaluation. The AG clinical studies in breast cancer serves as a reference pathology unit and tumor bank for the ADAPT-TN-III trial.
WSG ADAPT-HER2-IV (2024-2026)
This clinical trial of the West German Study Group (WSG) aims to optimize the treatment of HER2-positive early breast cancer. ADAPT-HER2-IV will compare neoadjuvant treatment with trastuzumab-deruxtecan (T-DXd) versus standard-of-care therapy (for instance neoadjuvant paclitaxel + trastuzumab + pertuzumab). Primary end points include pCR-rates and 3-year distant-disease-free survival (dDFS). ADAPT-HER2-IV is a prospective, multicenter, randomized open-label Phase-II trial. More than 400 breast cancer specimens will be subjected to central pathology review. The AG clinical studies in breast cancer serves as a reference pathology unit and tumor bank for the ADAPT-HER2-IV trial.
WSG ADAPTcycle (2020-2023)
This clinical trial of the Westgerman Study Group (WSG) implements an adjuvant dynamic marker-adapted personalized therapy (ADAPT) and compares endocrine therapy plus ribociclib (CDK4/6 inhibitor) with endocrine therapy plus chemotherapy in hormone receptor-positive/HER2-negative early breast cancer with intermediate risk. ADAPT-cycle is a prospective, multicenter, randomized open-label Phase III study. More than 5500 breast cancer specimens will be subjected to central pathology screening and mor than 1600 patients will be randomized. The AG clinical studies in breast cancer serves as a reference pathology unit and tumor bank for the ADAPT-cycle trial.
Current basic science and translational research
Characterization of osteoclast-like giant cells in breast cancer (2024-2025)
Breast cancer with osteoclast-like giant cells (OGC cells) is a rare variant of invasive breast carcinoma. OGC cells do not belong to the population of carcinoma cells. Instead, OGC cells are derived from fused macrophages of the tumor stroma. The formation of OGC cells is induced by paracrine signals from neighboring mammary carcinoma cells. Little is known about these OGC cells, so far. This study aims to characterize the molecular phenotype of OGC cells in breast cancer. In particular, this project compares OGC cells in breast cancer with other types of giant cells found in a variety of inflammatory diseases, including tuberculosis and sarcoidosis.
GATA3 in collagenous spherulosis and adenoid cystic carcinoma of the breast (2023-2024)
Collagenous spherulosis (CS) is a benign mammary lesion. Its tumorigenesis is incompletely understood. CS often affects mammary lobules and is characterized by a mixture of epithelial cells with myoepithelial and luminal differentiation. Occasionally, CS mimics adenoid cystic carcinoma (ACC) of the breast. ACC is a rare carcinoma of the mammary gland that belongs to the spectrum of triple-negative tumors. GATA3 is a transcription factor expressed by mammary epithelial cells of luminal differentiation. The current study aims to compare GATA3 expression in CS and ACC and evaluates the potential utility of GATA3 as a new immunohistochemical marker to support the differential diagnosis between CS and ACC.
Lobular breast cancer metastasis to the colon (2022-2023)
In advanced stages, invasive lobular breast cancer (ILC) is associated with metastasis to the abdominal cavity, including the large bowl. ILC metastases to the bowl do not form a circumscribed mass, but induce diffusely scatter lesions that imitate the endoscopic picture of colitis. This project compiles a cases collection of ILC metastases to the large bowl. Next, this project investigates the histological and molecular changes in the large bowl affected by metastatic ILC.
Molecular studies
Determinants of endocrine resistance (Endores) (2017-2023)
Endocrine therapy to block the estrogen receptor pathway in breast cancer is highly effective, but its usefulness is limited by intrinsic and acquired resistance. In this molecular study, we utilize tumor specimens of breast cancer patients subjected to short-term endocrine therapy prior to surgery (WSG ADAPT trial). Suppression of tumor cell proliferation in post- relative to matched pre-therapeutic tumor specimens allows to classify patients and tumors as endocrine-responsive or non-responsive. To decipher molecular alterations associated with endocrine resistance, large cohorts of endocrine-responsive and endocrine-resistant tumors are subjected to a comprehensive, comparative molecular characterization. This research initiative is supported by a grant of the German Cancer Aid.
Molecular pathology of invasive lobular breast cancer (ILBC)
Lobular breast cancer is the most common special histological breast cancer subtype. Lobular breast cancer is driven by inactivation of the cell adhesion molecule E-cadherin. In our studies on lobular breast cancer, we investigate inasmuch the biology of these tumors is determined by the loss of E-cadherin. Secondary genetic alterations, growth characteristics and therapeutic responsiveness are of particular interest.
Molecular pathology of microglandular adenosis (MGA)
Microglandular adenosis is an unusual breast disease associated with an increased risk for invasive breast cancer. Microglandular adenosis has long been believed to be reactive lesions. Current studies have shown that microglandular adenosis is a neoplastic process instead. In this work, we characterize the molecular alterations in microglandular adenosis. Loss of luminal differentiation is of particular interest in this context.