Invasive lobular cancer of the breast (ILC) is responsible for more than its share of treatment failures. Long-term survival of women with classic ILC has not improved significantly over the past half century, despite major improvements in breast cancer therapy and diagnosis. Foote and Stewart considered lobular carcinoma in situ (LCIS) to be the precursor of ILC, and that the “the mass eruption of tumor cells” occurred through “some lytic action of the tumor cells, naturally not to be detected by anatomic study.” Ackerman and Del Regato accepted this proposed mechanism, concluding that ILC arises from the acinar epithelium of the breast lobule. Despite the absence of clear evidence, these speculations were accepted as established fact more than 70 years ago. An inconvenient observation, the lack of E-cadherin staining, was assumed to result from a “loss” of that protein during tumor development. Our research group, the Swedish Organized Service Screening Evaluation Group, has examined all histologically proven ILC cases from Dalana County Sweden diagnosed from 1996-2019 with follow-up to the end of 2021. Histopathologic study of large section (8x10 cm) pathology slides, imaging and molecular biomarkers of 329 consecutive diffuse form of ILC showed a macroscopic structure unlike breast cancers of epithelial origin, a 19-year survival (56 %), poorer than expected from the histochemical biomarkers, and a growth pattern closely resembling that of normal breast tissue, hindering mammographic detection. Our group considered that ILC may originate from mesenchymal hybrid cells through the process of mesenchymal-epithelial transition (MET). Our cell culture studies from typical ILC cases progressed through more than 10 cell cycles in one year’s time and produced cells with the properties of mesenchymal hybrid cells. Histopathology-breast imaging correlation indicated two ILC subgroups with separate sites of origin. The classic, diffuse type of ILC appears to evolve from the extralobular mesenchyme of the breast. A second subgroup appears to evolve from and generally remain within the intralobular mesenchyme of the breast, appearing as multiple small colonies, each surrounding the acini and terminal ducts of the lobule, which invariably have normal, non-malignant epithelium. This intralobular subgroup has distinctly different imaging biomarkers, appearing as a distinct tumor mass easily detected at mammography. The 231 consecutive intralobular cases had 84% survival at 19-year follow-up. Differentiating the two is difficult based on the limited field of view offered by the conventional 1x3 inch glass slides. However, low-power histopathology of large sections correlates well with imaging findings and assists in differentiating these two subtypes. This translational research is consistent with new directions in precision medicine. Conclusions: The accepted terminology and assumptions of the nature of “ILC” must be reconsidered if we are to improve the poor survival rate of this misunderstood malignancy. Therapies, such as radiation and chemotherapy, are effective in treating epithelial breast cancers but are less effective in treating classic ILC, possibly due to a stem cell origin. Likewise, the IHC biomarkers are less predictive of prognosis in classic ILC for the same reason. Further, surgical removal of this diffuse malignancy is often incomplete as the full disease extent is difficult to evaluate by any imaging technique. So long as this unusual breast malignancy is termed “classic diffusely infiltrating lobular carcinoma,” implying that it has its origin in the acinar cells of the terminal ductal lobular units (TDLUs), we are unlikely to achieve any real progress in our efforts to control it. Appreciation of its mesenchymal stem cell origin offers a radically new approach to research and treatment. Citation Format: Robert Smith, Renáta Bozó, Peter B. Dean, Katalin Ormándi, Olga Puchkova, Orsolya Oláh-Németh, István Balázs Németh, Zoltán Veréb, F. Lee Tucker, Amy Ming-Fang Yen, Li-Sheng Chen, Hsiu-Hsi Chen, András Vörös, László Tabár. Why Are We Failing to Cure So Many Cases of Lobular Breast Cancer? [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-02-19.

Breast radiologists and nuclear medicine specialists have updated their previous recommendation/guidance at the 5th Hungarian Breast Cancer Consensus Conference. They suggest to adopt this actual protocol for the screening, diagnostics and treatment of breast tumors, from now on. This recommendation includes the description of the newest technologies, the recent results of scientific research, as well as the role of imaging methods in the therapeutic processes and the followup. Suggestions for improvement of the current Hungarian practice and other related issues as forensic medicine, media connections, regulations, and reimbursement are also detailed. The guidance has been in agreement with the related medical disciplines.

Abstract Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term “invasive lobular carcinoma” implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial–mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype. Citation Format: Andras Voros, Laszlo Tabar, Renata Bozo, Orsolya Olah, Katalin Ormandi, Zoltan Vereb, Istvan Nemeth, Peter B. Dean, Olga Puchkova, Ming-Fang Yen, Li-Sheng Chen. Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-09.

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such event, we followed cytoplasmic aggregation of RPB1, the aggregation prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining – from biopsy samples taken before treatment – the effectiveness of neoadjuvant chemotherapy.

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining—from biopsy samples taken before treatment—the effectiveness of neoadjuvant chemotherapy.

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.

Breast radiologists and nuclear medicine specialists updated their previous recommendation/guidance at the 4th Hungarian Breast Cancer Consensus Conference in Kecskemét. A recommendation is hereby made that breast tumours should be screened, diagnosed and treated according to these guidelines. These professional guidelines include the latest technical developments and research findings, including the role of imaging methods in therapy and follow-up. It includes details on domestic development proposals and also addresses related areas (forensic medicine, media, regulations, reimbursement). The entire material has been agreed with the related medical disciplines.

Az emlőrákszűrés hatékonyságának javítására az elmúlt években számos technológiai fejlesztés történt, amelyek többsége elsősorban a mammográfiai vizsgálat kiegészítőjeként jelent meg. Az egyik ilyen, széles körben ismertté vált technológia az automatizált emlőultrahang. A jelen célzott irodalomkutatás célja, hogy bemutassa az automatizált emlőultrahang szűrési alkalmazásával kapcsolatos szakmai álláspontokat és iránymutatásokat, valamint összegezze a technológiával kapcsolatos vizsgálatokat leíró tudományos szakirodalmat. Az automatizált emlőultrahangra vonatkozó információk összegyűjtésére célzott irodalomkutatást végeztünk. Publikusan elérhető online adatbázisokban kerestünk szakmai irányelveket és ajánlásokat, valamint tudományos közleményeket, amelyek az emlőrák szűrésével és korai felismerésével foglalkoztak. Az irodalmi áttekintés eredménye alapján kijelenthető, hogy az automatizált emlőszűrésről mint kiegészítő technológiáról denz emlő esetén, számos információ áll rendelkezésre, ugyanakkor az emlőrák szűrésével kapcsolatos irányelvek nem foglalkoznak még ezzel a technológiával. A célzott irodalomkeresés során 9 klinikai vizsgálatot tekintettünk át. Ezek többsége egykaros vizsgálat, viszonylag rövid követési idővel. A vizsgálatok többségét az USA-ban végezték. Az eredmények jellemzően emlőrákszűréssel kapcsolatos, rövid távú kimenetekre vonatkoztak: szenzitivitás, specificitás, daganatfelfedezési arány és visszahívási arány. A technológia legfontosabb előnyének az utólagos kiértékelés, valamint a reprodukálhatóság tekinthető. A vizsgálati eredmények arra utalnak, hogy denz emlő esetén a technológiának a mammográfia mellett történő, szűrési célú alkalmazása esetén növekszik az azonosított daganatok száma a mammográfia egyedüli használatához képest. Legfőbb hátránya ugyanakkor a megnövekedett visszahívási arány és az álpozitív esetek számának emelkedése. Összességében megállapítható, hogy az automatizált emlőultrahang emlőrákszűrési alkalmazásával kapcsolatos bizonytalanságnak a csökkentésére további tudományos bizonyítékokra van szükség. Orv Hetil. 2022; 163(35): 1374–1382.

Oncosurgical treatment of breast tumors involves the removal of metastatic axillary lymph nodes. In the last 30 years, the diagnosis and treatment of axillary lymph nodes have also undergone significant changes. The introduction of sentinel lymph node biopsy in 1993 made axillary block dissection with high morbidity safely omitted in a significant proportion of patients, and similarly, the staging of breast tumors and thus oncology and complex treatment became significantly more accurate. Shortly after the introduction of sentinel lymph node biopsy, intraoperative examination of sentinel lymph nodes (e.g. imprint cytology) also appeared, which significantly reduced the number of surgeries performed in the two sessions, thereby significantly reducing patient burden and surgical costs. The results of our study indicate that axillary block dissection is required in the treatment of axilla in an ever-decreasing group of patients and this proportion will decrease further in the future, with the increasing use of alternative axillary radiotherapy. The imprint cytological examination of sentinel lymph nodes taking into account current guidelines, no longer provides demonstrable benefits and its routine use is not justified. According to the latest international recommendations, intraoperative examination of the sentinel lymph node may be indicated in connection with mastectomy (when postoperative radiotherapy is not planned) and after neoadjuvant treatment. Our results suggest that the detection of suspected lymph nodes during preoperative axillary ultrasound may predict the stage of the disease. Based on our research results confirm that in patients receiving neoadjuvant therapy, in addition to the preoperative size of the tumour (≤20 mm, P = 0.002), the preoperative size of the lymph node (≤15 mm, P = 0.04) may also be used to predict that the stage of the disease is N0-1.

Several technological developments have been carried out recently to improve the effectiveness of breast cancer screening. Most of them have emerged as a complementary method to mammography. Automated breast ultrasound is one of these technologies. The objective of this study is to provide an overview on guidelines and recommenda-tions related to the application of automated breast ultrasound as a screening modality and to summarize the scien-tific literature. Targeted literature review was performed to collect information. We searched in publicly available databases for guidelines and recommendations as well as scientific publications on screening and early detection. We found substantial amount of information about automated breast ultrasound mainly for patients with dense breast; however, breast cancer screening guidelines have not yet incorporated this technology. 9 clinical studies were in-cluded in the review, most of them were single-arm studies with relatively short follow-up time. Most of them were performed in the USA. Results were presented mainly for short-term outcomes of breast cancer screening: sensitiv-ity, specificity, tumor detection rate and recall rate. The opportunity for retrospective evaluation of the images and the reproducibility are considered the most important advantages. Evidence suggest that the cancer detection rate can be improved compared to mammography alone in women with dense breast. The main disadvantages of this technology are the high recall and false positive rates. Further scientific evidence is required to reduce uncertainty related to the use of automated breast ultrasound for breast cancer screening.

Introduction: Based on international guidelines, axillary lymph node dissection (ALND) is recommended in cases of breast cancer if preoperative examinations confirm axillary metastasis. We examined which set of preoperative parameters might render ALND unnecessary. Patients and methods: Preoperative examinations (axillary ultrasound and aspiration cytology) confirmed axillary metastasis in 190 cases out of 2671 patients with breast cancer; primary ALN dissection was performed on these patients with or without prior neoadjuvant therapy. The clinico-pathological results were analysed to determine which parameter might predict the presence of no more than 2 or 3 metastatic ALNs. Results: The final histological examination confirmed 1-3 metastatic lymph nodes in ALND samples in 116 cases and over 3 metastatic lymph nodes in 74 cases. For patients receiving neoadjuvant therapy (59 out of the 190 cases), if the size of the primary tumour was 2 cm or smaller and/or the metastatic ALN was 15 mm or smaller, then the patient was likely to have no more than 3 positive ALNs (stage N0-1 disease) (p <0.001). If the patient did not receive neoadjuvant therapy, stage N2 or N3 disease was very likely. No correlation was found between other clinicopathological characteristics of the tumour and involvement of the ALNs. Conclusion: Axillary lymph node dissection is not necessary for selected breast cancer patients with axillary metastasis receiving neoadjuvant therapy. In these cases, sentinel lymph node biopsy with or without radiation therapy and close follow-up may serve as adequate therapy. (C) 2019 Published by Elsevier Ltd.

Breast radiologists and nuclear medicine specialists have updated their previous recommendation/guidance at the 4th Hungarian Breast Cancer Consensus Conference. They suggest to adopt this actual protocol for the screening, diagnostics and treatment of breast tumors from now on. This recommendation includes the description of the newest technologies, the recent results of scientific research, as well as the role of imaging methods in the therapeutic processes and the followup. Suggestions for improvement of the current Hungarian practice and other related issues as forensic medicine, media connections, regulations, and reimbursement are also detailed. The guidance has been in agreement with the related medical disciplines.

Background: According to international guidelines after positive preoperative axillary ultrasound (axUS) and axUS lymph node needle biopsy the axillary block dissection is recommended. More than half of the patients with preoperative US-guided biopsy proven axillary lymph node metastases had N1 disease. In these cases, the axillary block dissection is overtreatment. The purpose of our study was to investigate whether axUS and lymph node needle biopsy, combined with pathological and clinical factors could be used to identify axillary metastasis and preoperatively differentiate light versus nodal disease burden.

Background: By pursuiting modern surgical breast cancer therapy, there’s a need for using such imaging and reconstruction modalities which help us make a certain decision of the probability of breast conserving surgery or the extension of the axillar intervention.

Apocrine encapsulated papillary carcinoma (EPC) of the breast is a rare neoplasm, and only 10 cases have been reported in the literature to date. Although EPC by definition lacks a peripheral myoepithelial layer, all previously published apocrine EPC cases were clinically indolent and lacked a conventional invasive component. Herein, we report the 11th case of apocrine EPC, which had a conventional invasive carcinoma component and provides evidence of the malignant potential of this entity. We postulate that apocrine EPC is most likely a morphological variant of conventional EPC, with the same unpredictable malignant potential as non-apocrine cases.

Introduction: Intraoperative touch imprint cytology (TIC) of the sentinel lymph node(s) (SLN(s)) in the treatment of breast cancer has significantly reduced the number of axillary block dissections (ABD) required during second surgeries. Based on recent studies, ABD was not considered necessary if the presence of tumor cells/micrometastasis was confirmed in the SLN(s) or in the case of macrometastases in a patient group meeting the inclusion criteria for the ACOSOG Z0011 study. Our aim was to determine the sensitivity and usefulness of TIC with regard to these results.Methods: TICs of the SLN(s) were examined in 1168 patients operated on for breast cancer. The method was also analyzed retrospectively based on the guidelines for the Z0011 study. During TIC, new samples were cut every 250 pm; impression smears were evaluated after being stained with hematoxylin eosin.Results: TIC confirmed metastasis in 202 cases (202/1168, 17.29%). Metastasis was confirmed in SLN(s) in 149 additional cases during a final histological examination. The sensitivity of TIC was found to be 57.18%, and its specificity was 99.63%. An analysis was then performed except for cases that met the inclusion criteria for the Z0011 study and with metastasis smaller than 2 mm (micrometastasis/isolated tumor cells) considered to be positive during intraoperative cytology. The sensitivity of the method decreased to 34.23%, while its specificity was still high at 99.76%.Conclusions: Based on the new guidelines for ABD, imprint cytology cannot be considered a beneficial and cost-effective intervention in the surgical treatment of early breast cancer. (C) 2017 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.