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Background: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery. Methods: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen. Results: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101). Conclusion: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials. [ABSTRACT FROM AUTHOR]

Background: Desmoid type fibromatoses has proven to be a diagnostic and therapeutic challenge, as they often appear primarily as a carcinoma of the breast with a high recurrence risk. Patients: A digital archive search was performed for the period from 2009 to the end of 2018. Inclusion criteria consisted of histological examination of at least the surgical specimen in the reference pathology department and at least a second opinion diagnosis in the reference radiology department. Results: A total of 14 women and 1 man underwent surgery on desmoid type fibromatosisof the breast. The average patient age was 49 years (range: 22–72 years). The mean tumor size was 2.2 cm (range: 0.8–4.2 cm). The tumor was detectable in mammography in 12 out of 13 patients and in all 15 patients in sonography. MRI was performed preoperatively in 6 patients; in all of the patients, the tumor was visualized with inhomogeneous contrast enhancement. In the imaging procedures, all desmoid type fibromatoses were classified as suspicious. Performing the core biopsy, preoperative histology confirmed desmoid fibromatosis in 12 out of 15 patients. Nuclear stain for ß-catenin was positive in 7 out of 10 patients.Negative staining was found for AE1/A3 in 10 out of 10 and CD34 in 12 out of 12 patients. In all of the patients, a single-stage operation without the detection of border-forming tumor margins was performed. The follow-up interval ranged from 16 to 96 months (mean: 44.86 months, median: 43 months). In this follow-up period, no patient was diagnosed with desmoid tumor recurrence. Conclusion: In imaging, desmoid type fibromatosis of the breast has typical malignancy-related criteria. Extensive preoperative diagnostics enable the planning of complete primary excision of the lesion and reduce the recurrence risk. [ABSTRACT FROM AUTHOR]

Overexpression of CD24 is an independent prognostic factor for breast cancer. Recently, two polymorphisms in the CD24 gene were linked to disease risk and progression in autoimmune diseases. Here, we evaluated the clinical relevance of these polymorphisms with respect to their potential to predict a pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC), one of the strongest prognostic factors in this setting. A total of 257 patients were randomized to either doxorubicin/cyclophosphamide (AC) or doxorubicin/pemetrexed (AP), both followed by docetaxel (Doc) as NCT for T2-4 N0-2 M0 PBC as part of an international, multicenter, randomized phase II trial. CD24 polymorphisms were analyzed on germ line DNA and correlated with clinicopathologic variables and pCR. No significant associations were found between either of the polymorphisms and any of the clinicopathologic variables. In a multivariate analysis, CD24 Val/Val genotype was the only significant predictor of pCR (OR: 4.97; P = 0.003). The predictive potential was significant in both treatment arms and in the hormone receptor-positive subgroup. There was no correlation between CD24 3′UTR (TG/Del) genotype and pCR. We did not observe any association between CD24 genotype and CD24 protein expression or in vitro chemosensitivity, but there was a significant correlation between CD24 Val/Val and intratumoral lymphocyte aggregates. In conclusion, CD24 Ala/Val SNP is a strong and independent predictor of pCR after NCT for PBC and may affect immune functions rather than tumor characteristics. Further evaluation of the CD24 function and validation of its predictive potential are clearly warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common tumor-related cause of death in women in Europe and worldwide. The aim of our retrospective study, including 6654 women, was on the one hand to verify the validity of the worldwide known Nottingham prognostic index (NPI), and on the other hand to create a new model with even more prognostic validity. Our newly developed Altona prognostic index (API) shows significantly superior outcome in calculating progression free survival. In contrast to the NPI, the API considers characteristics such as subtypes of breast cancer, as this disease is heterogenous involving different entities, and patient's age. Evaluating progression free survival in different subgroups, our study shows that both these prognostic indices should only be applied on a patient collective that is ≤70 years old with first primary, unifocal, unilateral breast cancer that is of no special type (NST), estrogen receptor-positive and Her2-negative to get valid prediction data. Breast cancer is a heterogeneous disease representing a number of different histopathologic and molecular types which should be taken into consideration if prognostic or predictive models are to be developed. The aim of the present study was to demonstrate the validity of the long-known Nottingham prognostic index (NPI) in a large retrospective study (n = 6654 women with a first primary unilateral and unifocal invasive breast cancer diagnosed and treated between April 1996 and October 2018; median follow-up time of breast cancer cases was 15.5 years [14.9–16.8]) from a single pathological institution. Furthermore, it was intended to develop an even superior risk stratification model considering an additional variable, namely the patient's age at the time of diagnosis. Heterogeneity of these cases was addressed by focusing on estrogen receptor-positive as well as Her2-negative cases and taking the WHO-defined different tumor types into account. Calculating progression free survival Cox-regression and CART-analysis revealed significantly superior iAUC as well as concordance values in comparison to the NPI based stratification, leading to an alternative, namely the Altona prognostic index (API). The importance of the histopathological tumor type was corroborated by the fact that when calculated separately and in contrast to the most frequent so-called "No Special Type" (NST) carcinomas, neither NPI nor API could show valid prognostic stratification. [ABSTRACT FROM AUTHOR]

Amplification of genomic DNA encoding oncogenes such as HER-2 (syn. c- erbB/c-neu) may be substantially involved in the initiation and progression of breast cancer. In order to refine and facilitate the quantitative analysis of HER-2 amplification in breast cancer, differential polymerase chain reaction (PCR) was performed on DNA derived from single cryosections of tumor tissue. This technique is based on the simultaneous amplification of a potentially amplified oncogene (HER-2) and a reference gene (IFN-gamma). Differential PCR yielded reproducible results that were in agreement with gene copy quantification using the dot blot technique. Thus we suggest differential PCR to be a reliable and rapid method for determining relative gene dosage in a minute amount of tumour tissue. [ABSTRACT FROM AUTHOR]