Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2023.

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer.

Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023.

Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial.

Purpose: Tumor microenvironment (TME) immune markers have been correlated with both response to neoadjuvant therapy and prognosis in patients with breast cancer. Here, immune-cell activity of breast cancer tumors was inferred by expression-based analysis to determine if it is prognostic and/or predictive of response to neoadjuvant paclitaxel-based therapy in the GeparSepto (G7) trial (NCT01583426).

Experimental Design: Pre-study biopsies from 279 patients with HER2-negative breast cancer in the G7 trial underwent RNA-seq-based profiling of 104 immune-cell-specific genes to assess inferred Immune Cell Activity (iICA) of 23 immune-cell types.

Mismatch Repair Deficiency Drives Durable Complete Remission by Targeting Programmed Death Receptor 1 in a Metastatic Luminal Breast Cancer Patient.

Background: In the field of breast cancer tumor biology, triple-negative breast cancer patients are the main focus of current clinical trials exploring the use of immune checkpoint inhibitors due to higher frequencies of somatic mutations, neoantigens, and resulting tumor-specific T-cell reactivity.

Case Report: Here, we present the case of a 66-year-old woman with metastatic luminal breast cancer that rapidly responded to monotherapy with pembrolizumab, a monoclonal anti-PD-1 antibody. This patient obtained a partial clinical response within the first cycle of treatment and an ongoing durable complete remission after 12 weeks.

Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study.

Background: Earlier epidemiological studies indicate that associations between obesity and breast cancer risk may not only depend on menopausal status and use of exogenous hormones, but might also differ by tumor subtype. Here, we evaluated whether obesity is differentially associated with the risk of breast tumor subtypes, as defined by 6 immunohistochemical markers (ER, PR, HER2, Ki67, Bcl-2 and p53, separately and combined), in the prospective EPIC-Germany Study (n = 27,012).

Methods: Formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 657 incident breast cancer cases were used for histopathological analyses.

Comparison of molecular abnormalities in vulvar and vaginal melanomas.

Malignant melanoma of the vulva and vagina is relatively uncommon and accounts for <5% of all melanomas in women. The aim of our study was to establish the biological properties and evaluate potential therapeutic targets in these tumors. We collected a series of 65 cases from three centers and re-evaluated the tumor tissue for predominant growth pattern (superficial spreading, nodular, and mucosal lentiginous) and tumor thickness.

Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay.

It has been hypothesized that carcinoma metastasis is initiated by a subpopulation of circulating tumor cells (CTCs) found in the blood of patients. However, although the presence of CTCs is an indicator of poor prognosis in several carcinoma entities, the existence and phenotype of metastasis-initiating cells (MICs) among CTCs has not been experimentally demonstrated. Here we developed a xenograft assay and used it to show that primary human luminal breast cancer CTCs contain MICs that give rise to bone, lung and liver metastases in mice.

Transitions between flat epithelial atypia and low-grade ductal carcinoma in situ of the breast.

Flat epithelial atypia (FEA) of the breast typically is a localized alteration involving only few, neighboring terminal ducto-lobular units. However, occasionally there are cases with extensive FEA and morphologic evidence of direct transitions between FEA and classical low-grade ductal carcinoma in situ (lg-DCIS). To investigate the relationship between FEA and DCIS in these cases, we microdissected multiple foci of the respective lesions in a series of 10 cases and performed comparative allelotyping using a panel of 14 loss of heterozygosity markers.

Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues.

A shot in the arm for cancer treatment: two MUC1 tetanus toxoid vaccines were synthesized and induced a strong immune response in mice. The antibodies elicited by the vaccines show a high selectivity for the tumor cells in mammary carcinoma tissues and also distinguish between tumor tissues at different stages.

Reduction of CD44(+)/CD24(-) breast cancer cells by conventional cytotoxic chemotherapy.

Breast cancer cells with the CD44(+)/CD24(-) phenotype have been associated with stem cell properties. To analyze effects of cytotoxic chemotherapy on these cells, we examined a series of 50 breast carcinomas before and after neoadjuvant chemotherapy with epirubicin/cyclophosphamide using double immunofluorescence. Before treatment, an average of 4.

Invasive ductal breast cancer within a malignant phyllodes tumor: case report and assessment of clonality.

Invasive carcinomas arising within fibroepithelial tumors represent an uncommon manifestation of breast cancer. We report the case of a 70-year-old woman who underwent mastectomy for a malignant phyllodes tumor measuring 6 cm. Histological workup of the specimen revealed a high-grade invasive ductal carcinoma 2.

Invasive tubular carcinoma of the breast frequently is clonally related to flat epithelial atypia and low-grade ductal carcinoma in situ.

Low-grade precursor lesions, such flat epithelial atypia (FEA), low-grade ductal carcinoma in situ (lg-DCIS), and lobular neoplasia (LN) often coexist with invasive tubular carcinomas (TCs) of the breast. To evaluate a possible clonal relationship, we have examined a series of 27 TC and the surrounding putative precursor lesions using loss of heterozygosity analysis and mitochondrial DNA sequencing. In these lesions (22 FEA, 10 lg-DCIS, 3 LN), loss of heterozygosity was most frequently observed on the long arm of chromosome 16 as well as at chromosome 8p21, 3p14, 1p36 and 11q14 with a high degree of homology of allelic losses between FEA, lg-DCIS and tubular carcinomas.

Estrogen-related receptor alpha expression and function is associated with the transcriptional coregulator AIB1 in breast carcinoma.

The significance of the estrogen-related receptor alpha (ERRalpha) as prognostic marker for poor clinical outcome in breast carcinoma has recently been reported. Transcriptional activity of nuclear receptors such as ERRalpha depends on coregulatory proteins. Thus, we compared the expression of different receptors, coregulators, and target genes on RNA and protein level in identical primary breast tumor samples (n = 48).

The histone acetyltransferase hMOF is frequently downregulated in primary breast carcinoma and medulloblastoma and constitutes a biomarker for clinical outcome in medulloblastoma.

Loss of H4 lysine 16 (H4K16) acetylation was shown to be a common feature in human cancer. However, it remained unclear which enzyme is responsible for the loss of this modification. Having recently identified the histone acetyltransferase human MOF (hMOF) to be required for bulk H4K16 acetylation, here we examined the involvement of hMOF expression and H4K16 acetylation in breast cancer and medulloblastoma.

Clonality of lobular carcinoma in situ (LCIS) and metachronous invasive breast cancer.

Lobular carcinoma in situ (LCIS) of the breast is generally considered an indicator for a bilaterally increased risk of invasive breast cancer (IBC). However, as recent studies suggested a clonal relationship between a subset of synchronous LCIS and invasive lobular carcinomas (ILC), we aimed to examine a possible precursor role for LCIS and IBC occurring in the same breast at a later time. Out of a consecutive series of 88 LCIS, nine patients developed IBC (5 ILC and 4 invasive ductal carcinomas) between 2 and 10 years after initial biopsy.

Immunohistochemical and cytogenetic characterization of acantholytic squamous cell carcinoma of the breast.

Primary acantholytic squamous cell carcinoma (ASCC) of the breast is a rare and aggressive variant of invasive breast cancer. Here we report two new cases of ASCC and their immunohistochemical and cytogenetic characterization. One case was associated with systemic metastases and death and the other with local failure prior to loss of follow-up.

CTCF gene mutations in invasive ductal breast cancer.

The CTCF gene encodes for a transcriptional repressor of the c-myc oncogene and has previously been mapped to one of the smallest regions of overlapping interstitial deletions on chromosome 16q22.1 in invasive breast cancer. This chromosomal region is frequently deleted in both invasive lobular and ductal breast carcinomas.

C-myc oncogene amplification in ductal carcinoma in situ of the breast.

The c-myc oncogene is frequently activated in invasive breast cancer and has been associated with high nuclear grade, lymph node metastasis and poorer disease outcome. We have examined c-myc oncogene amplification using fluorescence in situ hybridization in a series of 96 pure DCIS. Additionally we assessed amplification and expression of the Her2 and bcl-2 oncogenes.