Multicentric Breast Cancer Research Articles

A unified approach for breast cancer discrimination using metasurface-based microwave technology

Multifocal (MF) and multicentric (MC) breast cancers are more likely to be aggressive than unifocal (UF) breast tumors, and they are linked to high recurrence probability, lymph node metastases, and low survival rates. Metastasis is the process through which cancer cells spread to different body areas. Although the longevity of patients with metastatic breast cancer is high, it is restricted by the growth of brain metastases. Medical imaging techniques have inherent limits. Hence, a precise and sensitive substitution is required. Because microwave imaging is portable, non-ionizing, and affordable, it has become a viable method for the detection of breast cancer. As far as we know, this is the first research aiming at discriminating MF and MC breast cancers from UF ones. This proposal presents a 2×2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2\ imes 2$$\\end{document} planar metasurface-based array antenna in the Industrial Scientific Medical frequency band at 2.4 GHz. The proposed array configuration significantly enhanced the gain to 4 dBi rather than a single element at 50 Ω. The geometric arrangement of the four antenna elements is optimized to discriminate the critical stage of breast cancers (UF, MF, or MC). As the proposed structure does not surround the breast, it contributes to a higher degree of comfort than the conventional antenna configurations. The magnitude and phase of S-parameters of the backscattered signals are analyzed in this research.

Abstract PO5-20-08: A Case of Multifocal Ductal Breast Carcinoma with Extension into Lobules and Concurrent Primary Colon Adenocarcinoma

Abstract Background Multifocal (MF) multicentric breast cancer is a form of breast cancer that consists of disease independently developing at various locations due to a tumor clone spreading within the ductal complex. Multifocal breast cancer is associated with increased local recurrence. Our case highlights an example of multifocal breast cancer and addresses treatment challenges. Case presentation The patient is a 52-year-old African American female with a history of HCV cirrhosis, diabetes mellitus, and hypertension who presented with a palpable 4 cm right breast mass, without adenopathy, clinically Stage II, T2N0. Mammogram revealed a 2.5 cm right breast mass and three right level 1 axillary nodes with biopsy confirming invasive ductal carcinoma with extension into the lobules, ER positive (3%)/PR-/HER2-, Ki-67 95%. Neoadjuvant paclitaxel, carboplatin, and pembrolizumab was initiated but she incurred complications of decompensated liver cirrhosis after the second cycle and treatment was held. After 2 cycles her tumor was not palpable, and surgery was recommended, but due to COVID infection and concurrent decompensated liver failure surgery management was delayed. She underwent staged surgery with partial mastectomy without lymph node exploration. Histopathology showed DCIS grade 3 with extension into lobules and invasive ductal carcinoma with no lymphovascular invasion and all margins were negative, pathological stage ypT3NxM0. Immunohistochemistry demonstrated partial ER+ (50%)/PR-/HER2-, Ki-67 80%. She was given 4 cycles of adjuvant cyclophosphamide, adriamycin, pembrolizumab and continued on maintenance pembrolizumab. The patient was found with anemia out of proportion to chemotherapy and underwent colonoscopy that showed a colonic mass. Biopsy showed a primary moderately differentiated colonic adenocarcinoma. Her re-excision with new margins for partial mastectomy had negative margins, and 2 negative sentinel lymph nodes for ypN0. Genetic testing was negative. She continued on adjuvant immunotherapy with pembrolizumab for breast cancer. She is planned to start on adjuvant anastrozole. Patient has completed adjuvant radiation treatment and has no new complaints. She is pending curative intent completion colectomy for colon cancer. Discussion This case of MF breast cancer is significant, as one foci was ER negative, which responded to neoadjuvant chemoimmunotherapy and other ER positive that did not respond to treatment and was surgically excised. The pathology report from the surgical specimen revealed DCIS with extension into the lobules. Due to her tenuous clinical condition, she had staged surgeries for breast cancer, and now colon cancer. Genetic testing is negative. Currently, there is insufficient data to suggest which surgical approach is preferred in MF breast cancer. Based on the literature, breast conservation therapy (BCT) is a feasible option and is oncologically safe. Due to the patients’ medical condition and infections, it was felt a less invasive surgery could offer cure and minimize complications. Our patient underwent neoadjuvant chemoimmunotherapy, followed by partial mastectomy, adjuvant chemoimmunotherapy, second staged completion breast surgery, radiation therapy, and anti-estrogen therapy. MF breast cancer is associated with increased lymph node involvement. A 2022 meta-analysis found that multifocal and multicentric breast cancer has a slightly increased risk of death as compared to unifocal tumors. Lastly, our patient is African American, and multifocal tumors occur with a higher incidence in African Americans (43.4%) and Asian patients (37%) as compared to whites (28.9%). This case of breast cancer highlights treatment challenges in a case of multifocal multicentric breast cancer occurring concurrently with a secondary primary colonic cancer. Citation Format: Rabab Jafry, Hina Khan, Jessica Jones. A Case of Multifocal Ductal Breast Carcinoma with Extension into Lobules and Concurrent Primary Colon Adenocarcinoma [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 PO5-20-08.

Current status of local treatment for multifocal / multicentric breast cancer

The detection rate of multifocal / multicentric breast cancer (MMBC) is increasing, and the local treatment of MMBC is attracting more attention. Relevant research focuses on the selection of surgical methods, the application of radiotherapy, and the feasibility of local ablation. Currently, due to the high rate of local recurrence in breast conserving surgery, most Chinese doctors recommend mastectomy to patients with MMBC. Recent studies have shown that with the development of imaging technology, surgical techniques, accurate judgment of the resection margin, the emergence of new therapeutic drugs and the improvement of the accuracy of radiotherapy, for eligible patients with MMBC, breast conserving surgery did not increase the local recurrence rate while ensuring negative margin and cosmetic results. Whether patients with MMBC must receive adjuvant radiotherapy after mastectomy is controversial, with some evidence suggesting that MMBC may increase the risk of local recurrence and should be an important consideration for radiotherapy, and there is also evidence that the local recurrence rate of MMBC was higher regardless of the type of surgery. In general, the local treatment modality for MMBC is essentially the same as that for unifocal breast cancer, but more prospective studies are needed for further evaluation.

Characteristics of multifocality/multicentricity in breast cancer and its effect on axillary lymph node metastasis

Multifocal (MF) and multicentric (MC) breast cancers are seen with increasing frequency with advances in imaging methods. However, there is no consensus on the behavior and management of these tumors. In this study, we aimed to investigate the characteristics of MF/MC breast cancers and their relationship with axillary lymph node metastasis (ALNM). Patients who underwent surgery for breast cancer between January 2015 and January 2023 were retrospectively scanned. Exclusion criteria were as follows; male breast cancer, second primary cancer diagnosis, previous breast cancer history, previous excisional/incisional breast biopsy, neoadjuvant chemotherapy, and occult breast cancer. Multiple tumors that were closer than 5 cm to each other were defined as MF, and the others were defined as MC. T stage was determined in two different ways, using the largest tumor diameter (Tmax) and the aggregate tumor diameter (Tsum), and two different multivariate analysis models were applied. A total of 156 patients were enrolled in the study, including 130 unifocal (UF), 17 MF and 9 MC. Lymphovascular invasion (LVI) (p=0.43), ALNM (p=0.23), younger age (<50) (p=0.41) and invasive lobular carcinoma (ILC) (p<0.001) were higher in MF/MC tumors than in UFs. When comparing MF and MC, no difference was seen except progesterone receptor positivity (p=0.017). In both multivariate analyses, LVI and ILC had an effect on ALNM, while no effect of MF/MC was seen. In addition, while T stage had a significant effect on ALNM in the model using Tsum, it did not have a significant effect in the Tmax model. Our retrospective data supports that MF/MC is not a direct risk factor for ALNM and that the main factor affecting ALNM is the total tumor burden.

Performance of contrast-enhanced mammography for detecting multifocal and multicentric breast cancer and evaluating tumour size, and implications for surgical management: Early experience in a tertiary centre.

To compare diagnostic accuracy of contrast-enhanced mammography (CEM) with standard 2D digital mammography (equivalent to low-energy image; LEM) for detection of multifocal and multicentric breast cancer and evaluation of tumour size and disease extent for preoperative planning. Biopsy proven breast cancer patients who underwent CEM preoperatively between January 2021 and January 2023 were included in this study. CEM and LEM images were independently reviewed by at least two blinded readers. Lesion location, number, size (maximal diameter) and extension across the midline and/or nipple invasion were recorded. Tumour number and size estimated on imaging were compared with final operative histology, which served as the gold standard. Forty-nine patients (48 females and 1 male) and 50 cases (one patient had bilateral breast lesions) were included in the analysis. Median patient age was 60 (IQR 51, 69). CEM had significantly higher lesion detection rate compared with LEM, with sensitivities of 78% for LEM and 92% for CEM for the index tumour and 15% for LEM and 100% for CEM for multicentric and multifocal cancer. We found no statistically significant difference in median tumour size measurements on CEM and final surgical specimen (P value = 0.97); however, a significant difference was identified in the tumour size measured on LEM and surgical specimen (P value < 0.001). CEM is superior to standard 2D digital mammography for detection of multifocal and multicentric breast cancer and is a reliable and more accurate method for estimating tumour size.

Contrast-enhanced mammography versus breast MRI in the assessment of multifocal and multicentric breast cancer: a retrospective study.

Breast cancer multifocality and multicentricity diagnosis influences the surgeon's choice between applying breast conservative therapy or performing mastectomy. To assess the role of contrast enhanced mammography (CEM) and breast magnetic resonance imaging (MRI) in the assessment of preoperative breast cancer multifocality and multicentricity and to assess their accuracy, agreement and impact on the surgical management. The study retrospectively included cases over a 5-year period. After analysis and interpretation of suspicious breast lesions, a comparative evaluation of CEM and MRI was conducted with the assessment of diagnostic indices, including sensitivity, specificity and diagnostic accuracy. The kappa (κ) measure of agreement between both modalities was measured. The postoperative specimen pathology was the reference standard. One hundred and twenty-two female cases with 126 breast lesions were evaluated. Specimen pathology, MRI and CEM showed a single neoplastic lesion in 67.5%, 35% and 48.5% of cases, respectively, and multiple neoplastic lesions in 32.5%, 65% and 51.6% of cases, respectively. The sensitivity, specificity and accuracy of MRI were 95.12%, 49.41%,and 64.29%, and the CEM values were 85.37%, 64.71% and 71.43%, respectively. The κ value was 0.592 with an intermediate agreement between both modalities. When comparing between both modalities, enhancing foci showed a statistically significant difference, although there were no statistically significant difference in terms of high breast density or molecular subtype. In terms of breast cancer multifocality and multicentricity evaluation, MRI showed a higher sensitivity, while CEM showed a higher specificity, and there was moderate agreement between the two modalities.

Current Recommendations and Role of Breast Conservation Surgery for Multifocal or Multicentric Breast Cancer

Current Recommendations and Role of Breast Conservation Surgery for Multifocal or Multicentric Breast Cancer

Current understanding and distinct features of multifocal and multicentric breast cancers.

Multifocal (MF) and multicentric (MC) breast cancers are referred to as synchronous, multiple ipsilateral breast cancers; however, the definitions vary among the literature, which has made understanding and analyzing these diseases challenging. The incidence ranges from 1% to 60%, with a higher prevalence in pre-menopausal women. MF and MC breast cancers, compared with unifocal breast cancers, tend to be more aggressive and are associated with lower survival rates, higher recurrence, and lymph node metastasis. Typically, patients with MF/MC breast cancers are treated with radical surgery, while breast conservation therapy may also be considered. Investigations have focused on elucidating the distinct biological features of MF/MC breast cancers, including the clonality of the cancers, the genetic alterations, and the impact of these features on disease aggressiveness and patient prognosis. These findings will broaden the understanding of these breast cancer subtypes and aid in the development of more tailored treatment plans for patients.

Following in the footsteps of SABCS 2022: top 16 early breast cancer studies that could change our clinical practice: A review

A review of the studies presented at the SABCS 2022 conference on the treatment of breast cancer (BC) has been carried out; 16 of the most exciting and significant works reported at oral or poster sessions have been identified. Data from large randomized and population-based studies were presented, including TAM-01 (the role of adjuvant therapy with 5 mg tamoxifen for in situ cancer), six studies on the surgical treatment of early breast cancer, including a meta-analysis to assess the effect of surgery extent on overall survival, a comparison of the results of targeted lymph node dissection and biopsy of sentinel lymph nodes in patients after neoadjuvant systemic therapy, an analysis of the local relapse rate after breast-conserving surgery in patients with multicentric breast cancer, as well as the effect of carrier status of pathogenic variants of mutations in the ATM, BRCA1, BRCA2, CHEK2 and PALB2 genes on the occurrence of cancer of the contralateral breast. Among the systemic therapy studies, the 10-years results of APT trial, Peony trial were presented, as well as the results of the TMC analysis on the various roles of carboplatin addition in neoadjuvant chemotherapy regimens in patients younger and older than 50 years with triple-negative breast cancer, randomized clinical studies on the escalation of adjuvant endocrine therapy in high relapse risk groups (MonarchE and SWOG S1207), as well as new data on cognitive dysfunction after chemotherapy in patients in the RxPONDER trial. Also noteworthy are the reviews of treatment in special clinical situations: the first results of the POSITIVE trial (an assessment of the oncological and obstetric outcomes of interruption of adjuvant endocrine therapy for conception), an analysis of the mortality of males with breast cancer over the past 20 years, as well as an analysis of the methylmalonic acid effect on senile weakness in patients with early breast cancer.

Impact of multifocal or multicentric disease on local recurrence and survival in breast cancer patients with or without BRCA1/2 variants

Multifocal or multicentric (MFMC) breast cancer is mainly focused on breast cancer patients with unknown BRCA status, the incidence and clinical relevance of MFMC disease in BRCA1/2 carriers is less explored to date. Our study was to investigate the incidence of MFMC disease in BRCA1/2 carriers and whether MFMC disease influences local recurrence and clinical outcomes. In this retrospective study, 479 breast cancer patients with BRCA1/2 variants and 1437 age-matched noncarriers were enrolled and patients received either breast-conserving therapy (BCT) or mastectomy with or without radiotherapy. The rates of MFMC disease in BRCA1 and BRCA2 carriers, and noncarriers were 33.0% (61 of 185), 37.4% (110 of 294), and 31.2% (449 of 1437), respectively. MFMC disease in BRCA2 carriers was significantly higher than that in noncarriers (P = 0.039). After a median follow-up of 8.1years, among patients treated with BCT, BRCA2 carriers with MFMC disease experienced a significantly higher rate of ipsilateral breast tumor recurrence (IBTR) than those with unifocal disease (16.7% vs 4.1%, P = 0.044). Moreover, BRCA2 carriers with MFMC disease had a significantly worse RFS (unadjusted hazard ratio [HR], 3.65 [95% CI 1.40-9.52]; P = 0.008), DRFS (unadjusted HR, 3.07 [95% CI 1.07-8.80]; P = 0.037), and OS (unadjusted HR, 4.96 [95% CI 1.18-20.02]; P = 0.029) than those with unifocal disease when treated with BCT. MFMC breast cancer is more common in BRCA2 carriers, and BRCA2 carriers with MFMC disease treated with BCT exhibit a higher rate of IBTR and may have a poor survival.

Multifocal/multicentric breast cancer: Does each focus matter?

Multifocal (MF) and multicentric (MC) breast cancer cases have been increasingly diagnosed owing to the extensive use of improved preoperative breast imaging. The current tumor-node-metastasis staging system uses the dimension of the largest tumor and recommends reporting the pathological features of the largest tumor in MF/MC breast cancers. This study aimed to explore whether the largest or aggregate dimensions of MF and MC breast cancers can better predict tumor behavior. We also attempted to study the histological and biological heterogeneities of separate foci in MF and MC breast cancers to determine whether it was necessary to examine each lesion. We retrospectively analyzed 121 patients with MF/MC (103 with MF and 18 with MC) breast cancers and 484 patients with unifocal breast cancer who were treated at the First Affiliated Hospital of Nanjing Medical University. Two methods were used to record the T stage (using the dimensions of the largest lesion and aggregate dimensions of all lesions). The histological grade, immunohistochemical parameters, and molecular subtypes of the largest lesion and other lesions in MF/MC breast cancers were studied to assess intertumoral heterogeneity. The use of aggregate dimensions upstaged 63 patients with MF/MC breast cancers to a more advanced stage and removed the independent effect of cancer multiplicity on lymph node positivity compared with the use of the largest dimension. Mismatches were found in the pathological type (9.9%), histological grade (4.1%), and molecular subtype (8.3%) among different foci. The tendency of MF/MC breast tumors to metastasize may be related to tumor load, which can be better predicted by the aggregate dimensions of all foci. The use of the current staging systems may require further evaluation and modification. Intertumoral heterogeneity indicates the necessity for pathological and immunohistochemical assessments of each lesion in patients with MF/MC breast cancers.

A retrospective comparative cohort study of SEER database analysis of the prognostic value of breast-conserving surgery and mastectomy in patients with multifocal multicenter breast cancer.

The prognosis of multifocal multicentric breast cancer (MIBC) was related to many factors, and there are different recommendations for surgical approaches. We compare the effects of breast-conserving surgery (BCS) and mastectomy on the survival of multifocal multicenter breast cancer female patients. A total of 38,164 female patients with pathologically confirmed multifocal multicenter invasive breast cancer from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were extracted, and the effects of different factors on the survival of these patients were retrospectively analyzed. The patients were divided into a BCS group and a mastectomy group, and the differences of breast cancer-specific survival (BCSS) and overall survival (OS) were compared between the 2 groups. Of the 38,164 patients included in the analysis, 14,533 (38.08%) underwent BCS and 23,631 (61.92%) underwent mastectomy. Multivariate analysis showed that age, grading, staging, number of lesions, radiotherapy, and BCS would affect the independent factors of BCSS and OS in patients. The median follow-up time was 108 months [interquartile range (IQR): 64-162 months). Multifactorial Cox proportional model analysis of prognostic risk showed that BCS reduced BCSS in patients older than 70 years [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.2-1.53; P<0.001], stage I and II, positive hormone receptor (HR), all 2-3 lesions, no radiotherapy (HR: 1.46; 95% CI: 1.33-1.6; P<0.001) and no chemotherapy (HR: 1.42; 95% CI: 1.28-1.57; P<0.001); BCS also reduced OS in patients over 40 years of age, stages I, II, and IIIC, all molecular subtypes, all HR-positive or negative, 2-3 lesions, and no radiotherapy (HR: 1.38; 95% CI: 1.31-1.46; P<0.001) and no chemotherapy (HR: 1.36; 95% CI: 1.29-1.44; P<0.001) patients. Multivariate Cox regression showed that BCS is an adverse factor for BCSS [adjusted HR 1.2 (1.11-1.3), P<0.001] and OS [adjusted HR 1.24 (1.19-1.3), P<0.001]. In early, good prognosis, treatment-sensitive patients, there is no survival advantage for BCS and more BCSS and OS benefit for mastectomy patients.

Multicentricity in Different Molecular Subtypes of Breast Cancer: A Cross-sectional Study in Isfahan.

Breast cancer is the most common cancer leading to death in women. Women with multicentric breast cancer were reported more likely to have poor prognosis. Here, we decided to study and compare the frequency distribution of multicentricity in different subtypes of breast cancer. This is a cross-sectional study that was performed in 2019-20 on medical records and breast pathology reports of 250 patients who undergone mastectomy due to breast cancer. Demographic data of all patients including age, along with other medical data such as menstruation condition, breast cancer grade, multicentricity status, stage, and expression of estrogen receptor (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) receptors were collected from medical records. Samples were divided into four subtypes of Luminal B, Luminal A, HER2 expressing, and basal-like. The mean age of patients was 50.21 ± 11.15 years. Ninety-five patients (38%) had multicentricity and HER2 expressing (48.5%) and Luminal A (41.4%) were most common in patients with multicentricity. In addition, basal-like group presented with least multicentricity (13.5%) among the subtypes (P = 0.008). We also showed significant increased chances of multicentricity in Luminal B (odds ratio [OR] = 3.782) (P = 0.033), Luminal A (OR = 5.164) (P = 0.002), and HER2-expressing group (OR = 5.393) (P = 0.011). Taken together, we showed significantly increased chances of multicentricity in patients with HER2-expression, Luminal A, and Luminal B groups compared to basal-like group or triple negative. These results were in line with most previous studies; however, we showed higher rates of multicentricity among our population compared to some previous reports.

The epidemiological and clinicopathological characteristics of multifocal/multicentric breast cancer in the Egyptian Delta and its impact on management strategies.

Multifocal (MFBC)/multicentric (MCBC) breast cancer is being more recognized due to the improved imaging modalities and the greater orientation with this form of breast cancer, however, optimal surgical treatment, still poses a challenge. The standard surgical treatment is mastectomy, however, breast-conserving surgeries (BCS) may be appropriate in certain situations. A total of 464 cases of MF/MCBC out of 4798 cases of breast cancer were retrospectively analyzed from the database of the Oncology Center, Mansoura University (OCMU), between January 2008 and December 2019. Radiologic involvement of multiple quadrants was reported in 27.9% by ultrasonography, 19% by mammography, and 59.1% by magnetic resonance imaging. BCS was performed in 32 cases (6.9%) while 432 cases underwent a mastectomy. Postoperative pathology revealed infiltration of other quadrants grossly in 23.5%, and under the microscope in 63.6% of the examined cases. Mean disease-free and overall survival were 95.5 and 164.6 months, respectively. When compared with MFBC, MCBC showed higher pathologic tumor size (p <0.001), higher stages (p <0.001), higher recurrence rates (p =0.006), and lower DFS (P =0.009) but with similar OS (P =0.8). Mastectomy is still the primary treatment option for MCBC with higher recurrence rates compared with MFBC. However, BCS for properly selected MFBC is considered oncologically safe, following the same rules of breast conservation for unifocal disease.

Association of Molecular Biomarker Heterogeneity With Treatment Pattern and Disease Outcomes in Multifocal or Multicentric Breast Cancer

PurposeThis study aimed to evaluate the rates of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 heterogeneity in multifocal or multicentric breast cancer (MMBC) and its association with treatment pattern and disease outcomes.MethodsMMBC patients with ER, PR, HER2, and Ki67 results for each tumor focus were retrospectively analyzed using Kappa test and categorized into the homogeneous group (Homo group) and the heterogeneous group (Hetero group). Chi-square tests were performed to compare the clinical features and treatment options between the groups. Disease-free survival (DFS) and overall survival (OS) rates were estimated from Kaplan–Meier curves and compared between two groups.ResultsA total of 387 patients were included, and 93 (24.0%) were classified into the Hetero group. Adjuvant endocrine therapy was more frequently assigned for patients in the Hetero group than in the Homo group (84.9% vs. 71.7%, p = 0.046). There was no difference in terms of adjuvant anti-HER2 therapy (28.3% vs. 19.6%, p = 0.196) and chemotherapy (69.9% vs. 69.8%, p = 0.987) usage between the two groups. At a median follow-up of 36 months, DFS rates were 81.2% for the Hetero group and 96.5% for the Homo group (p = 0.041; adjusted HR, 2.95; 95% CI, 1.04–8.37). The estimated 3-year OS rates for the groups were 95.8% and 99.5%, respectively (p = 0.059; adjusted HR, 5.36; 95% CI, 0.97–29.69).ConclusionHeterogeneity of ER, PR, HER2, or Ki67 was present in 24.0% patients with MMBC. Biomarkers heterogeneity influenced adjuvant endocrine therapy usage and was associated with worse disease outcomes, indicating further clinical evaluation.

Global variations in the definition and management of multifocal and multicentric breast cancer: the MINIM international survey.

The aim of this survey was to understand variation in the definition and management of multifocal and multicentric breast cancer globally. Some 743 physicians from 100 countries responded to this survey, which has provided a clear snapshot of international practice that can inform future work in this area. There is variation in the definition and management of multifocal/multicentric breast cancer among the international breast surgical community, the most controversial aspect being the use of MRI.

Does focal heterogeneity affect survival in postoperative ipsilateral multifocal and multicentric breast cancers?

In multicentric/multifocal breast tumors, there may be immunological and histological differences between foci that may affect survival and treatment choice. We aimed to evaluate the effect of focal heterogeneity seen in multicentric/multifocal breast tumors on survival. We retrospectively collected and analyzed the clinicopathological data of 89 female patients with multifocal/multicentric breast cancer, whose surgical and medical treatment was completed and who were followed up for 5 years. Of all patients, 29.2% (26/89) were heterogeneous. Heterogeneity of these foci was as follows: histologic heterogeneity of index foci (mix type): 15.7% (14/89), histologic heterogeneity of inter-foci: 7.9% (7/89), and immunohistochemical heterogeneity of inter-foci: 10.1% (9/89). When additional foci were evaluated, oncological therapy was changed for 3 (3.3%) of 89 patients. Heterogeneity does not have a significant (p>0.05) effect on recurrence and survival in multicentric/multifocal breast cancers. Pathological N stage is an independent risk factor for disease-free survival (hazard ratio=2.29, 95% confidence interval=1.39-3.76, p=0.001). In multifocal/multicentric breast cancers, less than 4% of patients may experience heterogeneity requiring change in the therapeutic decision. However, heterogeneity does not have a significant effect on recurrence and survival in multifocal/multicentric breast cancers. The pathological N stage is an independent risk factor for disease-free survival.

Abstract OT2-03-01: RNA disruption assay (RDA) - Breast cancer response evaluation for individualized therapy (brevity/brevity-02)

Abstract Background &amp; Rationale Identifying non-responders to chemotherapy with reliable predictive tests is crucial to response-guided neoadjuvant therapy. BREVITY aims to support RDA as a response assessment tool in breast cancer.RDA is based on RNA disruption, a qualitative and quantitative alteration of ribosomal RNA that correlates with chemotherapy response. RDA stratifies patients into 3 zones: non-response zone 1, partial-response zone 2 and response zone 3. Survival data in MA.22 trial showed significantly superior 5-year DFS KM-curves for zone 3 patients compared to zones 1 &amp; 2. MA.22 and other studies indicated a potentially valuable clinical utility to be pursued. Trial Design. Study type: Prospective 2-phase interventional study. Samples: 2 core needle biopsy specimens taken at 2 time points during chemotherapy. 1 Follow-up: 60 months from date of study enrolment. Incl. Criteria. •Women 18+ years old and able to provide informed consent. •Newly diagnosed clinical stage I, II or III breast cancer with complete surgical excision after neoadjuvant therapy as treatment goal. •Confirmation of invasive breast cancer of any subtype or grade, tumor size &amp;gt; 1cm. •Scheduled for neoadjuvant chemotherapy +/- antibodies and +/- other drugs according to SoC. •Willing to have research core needle biopsies at 2 timepoints during neoadjuvant treatment. Excl. Criteria. •Prior local or systemic therapy for current breast cancer. •Participation in another interventional clinical trial with experimental drugs during neoadjuvant therapy. •Stage IV breast cancer. •Bilateral, multifocal or multicentric breast cancer. •Prior malignant disease except curatively treated basalioma of the skin or pTis of the cervix uteri. •Pregnancy or breast feeding. Trial Objectives &amp; Endpoints Statistical Methods. Phase 1: training set will be used to estimate and visualize operating characteristics as functions of RDI. These include NPV, PPV, sensitivity, specificity, and related concepts. Suitable cut-offs will be determined that optimize NPV of zone 1 and PPV of zone 3. Phase 1 powered to estimate 25th RDI percentile as candidate for cut-off c1 with 9.5% precision E. Phase 2: analysis by interval-estimation of performance characteristics on an independent validation set, given cut-offs selected in phase 1. Primary target of validation is NPV of zone 1 that corresponds to RDA’s main clinical utility. PPV of zone 3 to be established for selected subgroups. Sample size for validation chosen to yield 95% CI estimate for NPV with 5.25% precision. Present and Target Accrual. Present AccrualTarget Accrual(must be fully evaluable). Phase 1 (Training set):71 (target 80). Phase 2 (Validation set):454 Other Contacts. Sponsor: Rna Diagnostics Inc Biopsy Collection Time Points for RDABiopsy(2 specimens)1st core biopsy2nd core biopsyTiming35 +/- 4 daysIf no drug change:55 +/- 5 days. If drug change:2-3 weeks after start of new drugs:•3-weekly: at 16 +/- 2 days•Bi-weekly: at day of 2nd dose•Weekly: at day of 4th dose Primary ObjectivesDescriptionEndpointsi.1.Phase 1: Determine 2 RDI cut-offs to have a diagnostic test optimized in terms of predictive values2.Phase 2: Establish performance characteristics for first cut-off in terms of NPVNPVPPVSecondary Objectivesi.Assess NPV in subgroups by subtypeNPVii.Assess PPV in HER2+PPViii.Compare pCR prevalence and DFS in zones 1-3 for all patients and by subgrouppCRDFSv.Test for association btw. cancer subgroups and test resultTest result (zones 1-3)vi.Compare RDA and other biomarker results (Ki67, tumor grade) Citation Format: Maureen Trudeau, Joke Tio, Foluso Ademuyiwa, Thierry Petit, Bryan Hennessy, Marina Cazzaniga, Daniele Generali. RNA disruption assay (RDA) - Breast cancer response evaluation for individualized therapy (brevity/brevity-02) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-03-01.

Ultrasonography increases sensitivity of mammography for diagnosis of multifocal, multicentric breast cancer using 356 whole breast histopathology as a gold standard

AbstractObjectiveThe purpose of this study is to evaluate effectiveness of ultrasonography and mammography for the detection of multifocal, multicentric breast cancers.Materials and MethodsA retrospective study was performed in 356 patients who underwent mastectomy. Preoperative diagnosis of malignant foci by ultrasonography and mammography were reviewed and compared with final pathological reports of the whole breast which was considered a gold standard.ResultsSeventy‐six patients (21.3%) had multifocal, multicentric cancers diagnosed from whole breast histopathology. Overall sensitivity for detection of additional tumour was 25.4% for mammography, 44% for ultrasonography. The sensitivity for combined methods was 50.8% (p &lt; .05).ConclusionUsing mammography and ultrasonography for preoperative diagnosis of breast cancer will miss almost half of cases with multifocal multicentric cancers. To achieve curative outcome when performing breast conserving surgery, preoperative investigation with only mammography and ultrasonography may be inadequate.

Utility of dual-energy contrast-enhanced spectral mammography for the diagnosis of multicentric breast cancer

Background. Breast cancer (BC) can be unifocal, multifocal, multicentric (MCBC) and bilateral according to number and localization of tumors. MCBC has different clinical and biological characteristics compared to unifocal BC, for example, a higher risk of lymph node involvement, a more aggressive natural history and a worse prognosis. Therefore, accurate diagnosis and detection of MCBC is one of the main tasks of imaging.Objective: to compare diagnostic accuracy of contrast enhanced spectral mammography (CESM) and digital mammography (DM) in the diagnosis of MCBC.Materials and methods. The study included 438 women with suspected BC. The results of DM and CESM were compared with the results of a pathomorphological study performed after surgery or biopsy to assess the effectiveness of imaging modalities. DM was performed for all women using a Senographe DS (GE, USA) unit. CESM was performed after intravenous injection of non-ionic contrast agents using injector with breast compression in the craniocaudal and mediolateral projections. The study was performed for both glands regardless of the location of the suspicious lesion in order to timely diagnose clinically asymptomatic bilateral cancer. The final diagnosis was made based on the results of the pathomorphological examination. MCBC was diagnosed when two or more tumors at a distance of 3 cm or more from each other were detected. Visualization of additional grouped calcifications of malignant type occupying a small portion of breast tissue (more than 15 pieces per 1 sq. cm) was considered as another mammographic sign of MCBC.Results. According to the pathomorphological examination BC was diagnosed in 154 (35 %) women out of 438 examined patients. MCBC was identified in 25 (16 %) of 154 patients. CESM was more effective than DM in detecting MCBC with sensitivity of 88.0 % vs 48.0 % (p = 0.002), accuracy of 92.2 % vs 90.9 %, negative predictive value of 97.6 % vs 90.8 % (p = 0.02), respectively. But the specificity was significantly higher in DM than in CESM – 99.2 % vs 93.0 % (p = 0.009), respectively, and the positive predictive value did not differ significantly (p = 0.12).Conclusion. CESM is a more sensitive method for diagnosing MCBC compared to DM with sensitivity of 88.0 % vs 48.0 %. The high negative predictive value of CESM (97.6 %) confirms the fact that this modality is an effective method for planning surgery and radiation therapy.