Multifocal Multicentric Breast Cancer Research Articles

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.

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.

Precision surgery for multifocal multicentric breast cancer in the genomic era

: Controversy exists with respect to appropriateness of breast conservation treatment (BCT) for multifocal multicentric breast cancer (MFMCBC). There is potential for the role of genomics to inform the extent of surgical therapy which should be undertaken for breast cancer. This review was conducted to clarify contemporary selection criteria for surgical therapy in patients with MFMCBC and to identify areas for future research. Contemporary efforts to tailor treatment using molecular technology have thus far centred on medical therapy. The use of genomics to direct surgical therapy has yet to gain comparable significance. At present, surgical treatment for MFMCBC is selected based on clinic-pathologic characteristics. Data suggests that genomics may predict response to neoadjuvant therapy for downstaging and margin status requirements to allow de-escalation of surgical treatment. There is room for future research relating to biomarkers and how genomic technology may impact the management of MFMCBC for individualized surgical therapy.

Multifocal and multicentric breast cancer, is it time to think again?

Multifocal multicentric breast cancer has traditionally been considered a contraindication to breast conserving surgery because of concerns regarding locoregional control and risk of disease recurrence. However, the evidence supporting this practice is limited. Increasingly, many breast surgeons are advocating breast conservation in selected cases. This short narrative review summarises current evidence on the role of surgery in multifocal multicentric breast cancer and shows that when technically feasible the option of breast conservation is oncologically safe.

Model observer for assessing digital breast tomosynthesis for multi-lesion detection in the presence of anatomical noise

Model observers are widely used in task-based assessments of medical image quality. The presence of multiple abnormalities in a single set of images, such as in multifocal multicentric breast cancer (MFMC), has an immense clinical impact on treatment planning and survival outcomes. Detecting multiple breast tumors is challenging as MFMC is relatively uncommon, and human observers do not know the number or locations of tumors a priori. Digital breast tomosynthesis (DBT), in which an x-ray beam sweeps over a limited angular range across the breast, has the potential to improve the detection of multiple tumors. However, prior studies of DBT image quality all focus on unifocal breast cancers. In this study, we extended our 2D multi-lesion (ML) channelized Hotelling observer (CHO) into a 3D ML-CHO that detects multiple lesions from volumetric imaging data. Then we employed the 3D ML-CHO to identify optimal DBT acquisition geometries for detection of MFMC. Digital breast phantoms with multiple embedded synthetic lesions were scanned by simulated DBT scanners of different geometries (wide/narrow angular span, different number of projections per scan) to simulate MFMC cases. With new implementations of 3D partial least squares (PLS) and modified Laguerre–Gauss (LG) channels, the 3D ML-CHO made detection decisions based upon the overall information from individual DBT slices and their correlations. Our evaluation results show that: (1) the 3D ML-CHO could achieve good detection performance with a small number of channels, and 3D PLS channels on average outperform the counterpart LG channels; (2) incorporating locally varying anatomical backgrounds and their correlations as in the 3D ML-CHO is essential for multi-lesion detection; (3) the most effective DBT geometry for detection of MFMC may vary when the task of clinical interest changes, and a given DBT geometry may not yield images that are equally informative for detecting MF, MC, and unifocal cancers.

Magnetic Resonance Imaging in the Pre-Surgical Staging of Breast Cancer: Our Experience

ABSTRACTPurpose: To investigate the clinical impact of magnetic resonance imaging (MRI) in the detection of multifocal–multicentric breast cancers, already identified by mammography and ultrasound, and analyzed histologically, to evaluate its role in preoperative staging. Materials and methods: From January 2012 to February 2014, 188 patients, aged 28 to 74 years, newly diagnosed with breast cancer on conventional imaging (mammography and ultrasound) were enrolled. They underwent preoperative contrast-enhanced 3T MRI. Patients underwent surgery according to international guidelines. Results of all diagnostic procedures were compared. Results: Among the 188 patients, 163 (87%) had a unilateral and unifocal tumor at both conventional imaging; MRI diagnosed 22/22 (100%) of multifocal and multicentric tumors, the combination of mammography and ultrasound diagnosed 12/22 (54%), and mammography alone diagnosed 8/22 (36%) multifocal and multicentric tumors. MRI prompted a change in surgical strategy in 10/188 (5%) patients. This change comprised mastectomy instead of conservative surgery (n = 7) and more extensive conservative surgery (n = 3). Conclusions: MRI was confirmed to show higher sensitivity than conventional imaging in detecting multifocal and multicentric breast cancers.

WE‐DE‐207B‐03: Influence of Local Anatomical Variations On Detection of Multifocal and Multicentric Breast Cancer

Purpose:We employed a novel model observer to assess the impact of local anatomic variations on the detection of multiple breast tumors depicted on mammograms. We expect the study to be valuable for future task‐based assessments and optimizations of x‐ray based breast imaging techniques (e.g., digital breast tomosynthesis for diagnosis of multifocal multicentric breast cancer (MMBC)).Methods:Regions of interest (ROIs) from four different sets of clustered lumpy background simulations were extracted as the image background. A random number of circular Gaussians were inserted to simulate cases with multicentric lesions. The task of the model observer was to perform a multiple‐lesion detection task, making both image‐level and location‐specific detection decisions based on the overall information from individual ROIs and their interactions. The detectability at each of the possible signal location was measured using channelized Hotelling observers with a novel implementation of partial least squares channels. The power law exponent β of local anatomical noise power spectrum, and spatial covariances K within the ROIs were computed to represent local background variations. The relationships between β, K and the detectability were evaluated.Results:β and/or K were different across the ROIs. Location‐specific signal‐to‐noise ratio (SNR) results showed statistically significant correlations between β, K and the detectability. Specifically, a ROI with a higher value of β, and/or K with larger and more variable off‐diagonal elements was associated with a lower SNR at that ROI. These results also demonstrate the potential of the model observer to adapt to the variations in anatomical backgrounds.Conclusion:We conducted a model observer study to explore the influence of local anatomical backgrounds on detecting MMBC. The study suggests that the optimal imaging settings may need to be adjusted when the clinical task of interest changes (e.g., find only the largest tumor versus find every tumor).This work is supported by National Science Foundation (NSF) Award CBET‐1445713.

Results by treatment modalities in multifocal/multicentric breast cancer: Retrospective analysis of 162 patients.

266 Background: The prognostic value of multifocal, multicentric breast cancer is still not well known. Although some studies have suggested that it is associated with a worst prognosis some have not suggest. We evaluated the effect of treatment modalities on overall survival and disease-free survival in breast cancer. Methods: One hundred and sixty two women with multifocal multicentric breast cancer diagnosed at our oncology center between January 2004 and December 2010 were retrospectively evaluated. Multifocality was defined as the presence of 2 or more foci of the tumor clearly separated in the same breast. Multicentricity was defined as the presence of 2 or more foci at different quadrants. Patients received neoadjuvant chemotherapy were excluded. Results: Median age of 162 women was 48 y ± 13,63 y. Eighty two of 162 patients were treated with breast-conserving surgery and 80 were treated with mastectomy. Radiotherapy was added to adjuvant therapy to patients with 4 or more positive axillary nodes and/or treated with breast conserving surgery. Three (1.8%) patients were excluded because of bilateral cancer and 1 (0.6%) was excluded because of Tx tumor. Eleven of 162 (6.7%) patients were not seen after surgery so data about adjuvant treatment was not known. Fifty of 147 patients were stage III, 68 were stage II and 30 were stage I. 27 (17.2%) patients received anthracycline based chemotherapy, 30 (20.3%) patients received hormonotherapy and 91 (56.1%) patients received taxane based chemotherapy. Trastuzumab added to the treatment at all patients, if HER2 neu-positive. Median follow up was 41 ± 4.1 (72-9 months) months. 30 systemic diseases at 24 patients were seen on follow up. 18 patients were in taxane group, 4 patients were in anthracycline group, 2 patients were in hormonotheraphy group. Nine patients were died in taxane group, 1 died in anthracycline group and 1 died in hormonotherapy group. Conclusions: Our retrospective analysis showed worst prognosis at taxane group but; patients with positive lymph nodes and perinodal invasion gets taxane based treatments. This retrospective analysis showed that systemic recurrence and survival in multifocal breast cancer are similar with unifocal disease.

Breast Conservation in Women with Multifocal-Multicentric Breast Cancer: Is It Feasible?

The incidence of preoperatively identified multifocal and multicentric breast cancer is rising with improved sensitivity of imaging modalities. Based on retrospective, historic data, breast conservation in women with multiple tumors has been discouraged because of high rates of local regional recurrence (LRR). These studies, however, do not extrapolate to contemporary practice as they do not incorporate the use of modern therapies and surgical techniques. This study is designed to evaluate the feasibility of breast conservation in women with multiple breast primaries. We retrospectively reviewed the charts of 22 women who underwent breast conservation surgery for 2 or more synchronous, ipsilateral cancers between 1998 and 2008. We extracted data including tumor size, nodal staging, receptor status, adjuvant therapies administered, and local-regional recurrence. A total of 22 patients were identified. Average follow up is 3.5years. One patient (4.5%) experienced an in-breast recurrence. Both initial tumors in this patient were invasive ductal carcinoma, ER/PR, negative and HER2 positive. Time to LRR was 2.5years. Our data are consistent with those of recent studies in which multifocal/multicentric local regional recurrence in multicentric/multifocal breast is equivalent to that seen in women with unifocal cancer. The single local recurrence in this study occurred in a premenopausal women with ER/PR- disease who were HER2+. Prior retrospective studies have identified ER/PR- and HER2 overexpression as independent risk factors for recurrence following breast conservation. Additional prospective trials are warranted to better assess the oncologic safety of breast conservation in this population.