Multicentric Breast Cancer Research Articles

Surgical Therapy for Women with Multiple Synchronous Ipsilateral Breast Cancer (MIBC): Current Evidence to Guide Clinical Practice

Based on retrospective, historic data, surgeons have long recommended mastectomy as the surgical approach for women with multiple ipsilateral synchronous (multifocal or multi-centric) breast cancer (MIBC). In the modern era, however, local recurrence rates have significantly decreased due to improved imaging techniques and earlier detection through breast cancer screening, more accurate delivery of radiation, and the advent of targeted systemic therapies. Given the significant non-surgical advancements in the field of breast cancer care, the role of maximally invasive surgery in improving breast cancer outcomes has diminished. This raises the question as to whether the routine recommendation for mastectomy in MIBC is rooted in current evidence or archaic data. This review summarizes data regarding surgical options for women with MIBC. The incidence of MIBC is increasing as a result of improved imaging modalities and the use of breast MRI for breast cancer screening and staging. MIBC tends toward more aggressive biology and higher rates of nodal positivity but recent data contradict the notion that more aggressive surgery improves outcomes. Retrospective studies and meta-analyses performed in the current era of targeted therapy and more sensitive breast cancer detection have demonstrated equivalent rates of local regional recurrence (LRR) in women with MIBC undergoing breast-conserving therapy (BCT) when compared stage to stage with women with unifocal disease. Alliance Z11102, the first national, prospective trial of breast conservation in the MIBC population in the USA, demonstrated the feasibility of BCT in this patient population with acceptable rates of conversion to mastectomy in the MIBC cohort. Prospective data regarding LRR and cosmetic outcomes for women undergoing BCT from completed clinical trials continue to mature, and new randomized clinical trials investigating the biology and treatment of MIBC are under design. The incidence of MIBC is increasing due to screening mammography, improved quality of imaging, and the utilization of breast MRI for breast cancer screening and staging. Local regional recurrence rates in women with unifocal disease have decreased due to earlier detection and improved regional and systemic therapy. As adjuvant therapy improves, the extent of surgery is less impactful on LRR and long-term survival. Current data demonstrate acceptable LRR in women undergoing BCT for MIBC for whom negative surgical margins are achieved and appropriate adjuvant therapy is administered. While additional prospective data regarding biology, LRR, cosmesis, and long-term survival in women with MIBC continue to be collected, current evidence supports the role of patient choice in deciding between breast conservation and mastectomy in this population.

The role of miRNAs as a predictor of multicentricity in breast cancer.

Expression profiles of miRNAs are shown to be different in various cancers to regulate expression of mRNA or to have a role in inhibition of translation, thus it shows the possible effect in progression, invasion and metastasis of breast cancer cells. The effect of breast conserving treatment in local recurrence and survival rates for the patients who have multicentric breast cancer is still controversial. In our study, we intended to evaluate the foresight of 84 miRNAs which are identified in breast cancer for having differentiated expressions. Thirty-one patients with unifocal and 26 patients with multicentric breast cancer were included in this study. These tissue samples of both malignant and normal breast tissues were kept in RNA later solution at - 80°C. Eighty-four miRNAs were studied with miScript miRNA PCR Array Human Breast Cancer kit. Fold change, cut off value was accepted as four. In unifocal group, there were 13 upregulated and five downregulated miRNAs and in multicentric group, there were three upregulated and seven downregulated miRNAs. To reach better results for breast cancer diagnosis and treatment, it is important to enlighten tumor biology, and pay attention to target and individual therapy. Thus, miRNAs have potential role in identifying tumor characteristics in supporting diagnosis and resulting with better evaluated disease for better treatment results with individual strategies.

Evaluating the current evidence to support therapeutic mammoplasty or breast-conserving surgery as an alternative to mastectomy in the treatment of multifocal and multicentric breast cancers.

The oncological safety of treating multiple ipsilateral breast cancers (MIBCs) with types of breast conserving surgery (BCS) compared to mastectomy remains uncertain. This is predicated on the absence of any randomised controlled trials or high-quality protocol defined prospective cohort studies. A single recently published systematic review by the first author, reports its summarised results in this review. Fundamentally the important question is the evaluation of clinical safety following BCS compared to mastectomy for treating MIBC, which is reported in only six studies. Consequently, current evidence doesn't support the latest St Gallen consensus suggesting the possibility of using BCS to treat all MIBC. There is minimal comparative outcomes data on multicentric (MC) cancers compared to multifocal (MF) cancers comparing BCS or mastectomy. There is also poor evidence of clinical outcomes following therapeutic mammoplasty (TM) for MIBC compared to mastectomy. The potential recommendation of two potential radiotherapy boosts to separate lumpectomy sites following BCS for MC cancers remains a novel treatment concept whose feasibility will be evaluated in the forthcoming NIHR funded randomised feasibility trial called MIAMI. This is a world first attempt to assess the feasibility of a randomised trial design alongside the on-going Alliance registry study (ACOSOG, American College of Surgeons Oncology Group Z11102) in the USA, in which there is no comparative evaluation of mastectomy outcomes. The MIAMI trial aims to assess the clinical safety of multiple lumpectomies combined with TM compared to the standard of mastectomy in MIBC stratified by MF or MC cancers. There is limited evidence on the impacts of inter-tumoral heterogeneity relating to breast cancer subtypes in relation to individualised treatments and recommendations for types of breast surgery. Recent studies have highlighted the potential contributions of stromal epigenetic changes that are currently poorly understood regarding their contributions to either clinical unifocal or MF cancers.

Prognostic impact of multifocal and multicentric breast cancer versus unifocal breast cancer.

The clinical behavior of multifocal and multicentric breast cancers (MMBCs) is not well characterized. We conducted this study to ascertain whether patients with MMBCs have a worse prognosis than patients with unifocal breast cancers (UBC). The subjects of this retrospective study were 734 consecutive patients who underwent definitive surgery for invasive breast carcinoma at our hospital between January 2004 and December 2006. MMBC was defined as ≥ 2 separate invasive unilateral breast tumors and pathological T stage was redefined based on the sum of the maximum diameter of each tumor. We evaluated disease-free survival (DFS) using the Kaplan-Meier method and Cox proportional hazards models. Of the 734 patients, 136 (18.5%) had MMBC. The pathological T stage of 36 of the patients with MMBC was upstaged by adopting the sum of each focus. MMBC did not have any survival impact, but MMBC upstaged by the modified pathological T stage was associated with worse DFS than non-upstaging MMBC (P = 0.004). Multivariate analysis revealed that upstaging MMBC was an independent factor for poor prognosis and worse DFS (HR 2.757, P = 0.043). MMBC itself may not be predictive of a worse prognosis; however, the sum of the invasive diameters of MMBC might be an important prognostic factor. Further studies are needed to confirm the prognosis associated with MMBC, taking into consideration the biological characteristics of each invasive focus.

New Approach to Oncoplastic Breast Conservation: Combining Autologous Volume Replacement and the Wise-pattern Mammaplasty.

Background:Oncoplastic breast-conserving surgery describes a set of techniques that allow for generous oncological resection with immediate tumor-specific reconstruction. These techniques are classically divided into either volume displacement (local breast flaps and or reduction mammaplasty/mastopexy strategies) versus volume replacement strategies (transfer of autologous nonbreast tissue from a local or distant site and, less commonly, implant placement). There have been few descriptions of merging these 2 classical approaches to facilitate breast-conserving surgery. The purpose of this report was to evaluate the efficacy of combining the most common oncoplastic volume displacement strategy (Wise pattern mammaplasty) with simultaneous autologous volume replacement from the lateral intercostal artery perforator (LICAP) flap to reconstruct the extensive partial mastectomy defect in patients with ptosis.Methods:A retrospective analysis of 25 consecutive patients with multifocal or multicentric breast cancers who underwent simultaneous volume replacement from the LICAP flap and volume displacement (Wise pattern mammaplasty) to achieve breast conservation was performed between January 2016 and January 2018. Clinical outcomes and postoperative complications were examined.Results:Twenty-five consecutive patients with a mean age of 56 years (range, 37–74 years) and mean body mass index of 28 kg/m2 (range, 22–37 kg/m2) all successfully underwent breast conservation by simultaneously employing the LICAP flap and Wise pattern mammaplasty to reconstruct the partial mastectomy defect. The average resection specimen weight was 220 g (range, 130–310 g) and average size of the malignancy resected was 6.5 cm (range, 3.7–9.2 cm). Three patients (12%) required re-excision for close or positive margins but were ultimately cleared. There were no complications related to the donor site. There were 4 patients (16%) with delayed wound healing related to the Wise pattern closure but no instances of LICAP necrosis or failure.Conclusions:The merger of Wise pattern volume displacement and autologous volume replacement techniques represents a novel strategy that is useful in the most challenging breast conservation patients with some degree of ptosis.

Interobserver Variation in Response Evaluation Criteria in Solid Tumors 1.1

Response Evaluation Criteria in Solid Tumors (RECIST 1.1) is the gold standard for imaging response evaluation in cancer trials. We sought to evaluate consistency of applying RECIST 1.1 between 2 conventionally trained radiologists, designated as A and B; identify reasons for variation; and reconcile these differences for future studies. The study was approved as an institutional quality check exercise. Since no identifiable patient data was collected or used, a waiver of informed consent was granted. Imaging case report forms of a concluded multicentric breast cancer trial were retrospectively reviewed. Cohen's kappa was used to rate interobserver agreement in Response Evaluation Data (target response, nontarget response, new lesions, overall response). Significant variations were reassessed by a senior radiologist to extrapolate reasons for disagreement. Methods to improve agreement were similarly ascertained. Sixty one cases with total of 82 data-pairs were evaluated (35 data-pairs in visit 5, 47 in visit 9). Both radiologists showed moderate agreement in target response (n = 82; ĸ = 0.477; 95% confidence interval [CI]: 0.314-0.640-), nontarget response (n = 82; ĸ = 0.578; 95% CI: 0.213-0.944) and overall response evaluation in both visits (n = 82; ĸ = 0.510; 95% CI: 0.344-0.676). Further assessment demonstrated "Prevalence effect" of Kappa in some cases which led to underestimation of agreement. Percent agreement of overall response was 74.39% while percent variation was 25.6%. Differences in interpreting RECIST 1.1 and in radiological image interpretation were the primary sources of variation. The commonest overall response was "Partial Response" (Rad A:45/82; Rad B:63/82). Inspite of moderate interobserver agreement, qualitative interpretation differences in some cases increased interobserver variability. Protocols such as Adjudication, to reduce easily avoidable inconsistencies are or should be a part of the Standard Operating Procedure in imaging institutions. Based on our findings, a standard checklist has been developed to help reduce the interpretation error-margin for future studies. Such check-lists may improve interobserver agreement in the preadjudication phase thereby improving quality of results and reducing adjudication per case ratio. Improving data reliability when using RECIST 1.1 will reflect in better cancer clinical trial outcomes. A checklist can be of use to imaging centers to assess and improve their own processes.

Systematic review of the impact of breast-conserving surgery on cancer outcomes of multiple ipsilateral breast cancers.

BackgroundThe clinical effectiveness of treating ipsilateral multifocal (MF) and multicentric (MC) breast cancers using breast‐conserving surgery (BCS) compared with the standard of mastectomy is uncertain. Inconsistencies relate to definitions, incidence, staging and intertumoral heterogeneity. The primary aim of this systematic review was to compare clinical outcomes after BCS versus mastectomy for MF and MC cancers, collectively defined as multiple ipsilateral breast cancers (MIBC).MethodsComprehensive electronic searches were undertaken to identify complete papers published in English between May 1988 and July 2015, primarily comparing clinical outcomes of BCS and mastectomy for MIBC. All study designs were included, and studies were appraised critically using the Newcastle–Ottawa Scale. The characteristics and results of identified studies were summarized.ResultsTwenty‐four retrospective studies were included in the review: 17 comparative studies and seven case series. They included 3537 women with MIBC undergoing BCS; breast cancers were defined as MF in 2677 women, MC in 292, and reported as MIBC in 568. Six studies evaluated MIBC treated by BCS or mastectomy, with locoregional recurrence (LRR) rates of 2–23 per cent after BCS at median follow‐up of 59·5 (i.q.r. 56–81) months. BCS and mastectomy showed apparently equivalent rates of LRR (risk ratio 0·94, 95 per cent c.i. 0·65 to 1·36). Thirteen studies compared BCS in women with MIBC versus those with unifocal cancers, reporting LRR rates of 2–40 per cent after BCS at a median follow‐up of 64 (i.q.r. 57–73) months. One high‐quality study reported 10‐year actuarial LRR rates of 5·5 per cent for BCS in 300 women versus 6·5 per cent for mastectomy among 887 women.ConclusionThe available studies were mainly of moderate quality, historical and underpowered, with limited follow‐up and biased case selection favouring BCS rather than mastectomy for low‐risk patients. The evidence was inconclusive, weakening support for the St Gallen consensus and supporting a future randomized trial.

Prognostic impact of multifocal and multicentric breast cancer compared with unifocal breast cancer.

e12614Background: The clinical behavior of multifocal and multicentric breast cancers (MMBCs) is not well characterized. The aim of this study was to assess whether patients with MMBCs have inferio...

Abstract OT2-01-05: Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer

Abstract Background: Sentinel lymph node biopsy (SLNB) by radioactively labelled 99mTechnetium +/- patent blue is so far the current standard in SLN detection. However, it remains a time- and cost-consuming procedure requiring the availability of a nuclear medicine department and a precise coordination with the subsequent surgery. It could be desirable to empower surgeons to be independent from availability of a nuclear source and to spare patients from radioactivity. Indocyanine green (ICG) as a fluorescent coloring agent is already known as safe in diagnostics for heart, circulation, liver and eye disease and may represent a valid alternative to 99mTc and patent blue (PBD), especially as it does not cause aesthetic impairment of the breast, with ICG being only visible with near infra-red light. Methods: This prospective, randomized study is a non-inferiority trial to evaluate ICG-fluorescence as an alternative to either 99mTc and/or patent blue dye for sentinel lymph node detection of primary breast cancer with and without neoadjuvant chemotherapy. Patients, aged 18 - 80 years, with unilateral or bilateral, unifocal or multifocal/ multicentric primary breast cancer without signs of metastases and written consent are eligible for this study. ECOG status of 0-2 and life expectancy > 1 year is required. All BMI classes are admitted to the study, with predefined subgroups of a) <= 20 b) >20-30 c) >30-40 d) >40. Tumor stages included are a) Tis (>= 4 cm) b) T1 c) T2 and d) T3. ICG-guided SLNB may be applied in patients in the following settings: a) before neoadjuvant, b) after neoadjuvant chemotherapy. Primary Endpoints: Rate of SLN detection by either of the methods in the following 3 arms of the trial: Arm A: 99mTc + patent blue dye (PBD) Arm B: 99mTc + indocyanine green (ICG) Arm C: Indocyanine green (ICG) Secondary Endpoints: - Time to identify (TTI) sentinel lymph node(s) (min) - Number of sentinel lymph nodes (SLN) and non-sentinel lymph nodes (non-SLN) - Rate of concordance of detection by 99mTc+patent blue dye (PBD) vs. 99mTc + ICG - Dose of radioactivity omitted in Arm C vs. Arm A & B Results: This trial is in progress. Citation Format: Kern P, Kimmig R, Rezai M, Hoffmann O, Bücker I, Braun M. Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-01-05.

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.

The identification of multifocal breast cancer-associated long non-coding RNAs.

To identify long non-coding RNAs (lncRNAs), which may be associated with multifocal and multicentric breast cancer (MMBC) by analyzing the differential expression of non-coding RNA in MMBC and unifocal breast cancers (UBC). 156 cases of invasive MMBC patients (136 patients with 2 focuses and 20 patients with 3 focuses) and 130 cases of UBC were collected from January 2005 to December 2015 in Yantai Yuhuangding Hospital. The differentially expressed lncRNAs in MMBC and UBC were screened by gene chip. RT-PCR was used to verify the differentially expressed lncRNAs. Significantly different expression was found in 1080 lncRNAs between MMBC and UBC (FC > 4, p < 0.05), among which, 458 were upregulated and 622 were down-regulated. In homologous lncRNAs, the expression levels of four lncRNAs including C19orf33, C3orf52, C15orf48 and C4orf19 in MMBC tissue were significantly different than those in UBC tissues. RT-PCR verified that the expression of C19orf33, C3orf52 and C15orf48 in MMBC tissue was significantly up-regulated and the expression of C4orf19 was significantly down-regulated, which was consistent with that of gene chip. C19orf33, C3orf52, C15orf48 and C4orf19 may have important functions in MMBC, and may be used as markers for MMBC.

Integrating anatomy, radiology, pathology, and surgery: An alternative approach in resecting multifocal and multicentric breast carcinoma.

The sick lobe hypothesis provides the basis for a lobar approach in radiology, pathology, and surgical treatment of breast cancer. This approach aims to remove the tumor together with the surrounding field of genetic aberrations. Detailed preoperative lobar imaging that properly maps the disease and assesses its extent guides the parenchymal resection. Integration of our knowledge of breast anatomy and pathology with the results of preoperative radiological mapping is critical in assessing the eligibility of patients with multifocal and/or multicentric breast cancer for breast conservation treatment. Through an appropriately selected incision, a multisegment resection of the diseased lobe(s) is performed, which leaves the residual parenchyma in a formation that allows dovetailing of one part into the other, like the way pieces of a jigsaw puzzle fit together. Detailed pathologic analysis of the surgical specimen provides valuable feedback to the radiologist, establishes the completeness of surgical intervention, and generates predictive information for therapeutic decisions. Our approach is a step in continuous search for ideal tailored therapy to avoid under or over-treatment of breast cancer patients.

Additional value of diffusion-weighted imaging to evaluate multifocal and multicentric breast cancer detected using pre-operative breast MRI.

To investigate whether diffusion-weighted imaging (DWI) aids pre-operative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate additional lesions in breast cancer patients. DCE-MRI and DWI were performed on 131 lesions, with available histopathological results. The apparent diffusion coefficient (ADC) of each lesion was measured, and the cut-off value for differentiation between malignant and benign lesions was calculated. A protocol combining the ADC cut-off value with DCE-MRI was validated in a cohort of 107 lesions in 77 patients. When an ADC cut-off value of 1.11 × 10-3 mm2/s from the development cohort was applied to the additional lesions in the validation cohort, the specificity increased from 18.9% to 67.6% (P < 0.001), and the diagnostic accuracy increased from 61.7% to 82.2% (P = 0.05), without significant loss of sensitivity (98.6% vs. 90.0%, P = 0.07). The negative predictive values of lesions in the same quadrant had decreased, as had those of lesions ≥1 cm in diameter. The ADC cut-off value in the validation cohort was 1.05 × 10-3 mm2/s. Additional implementation of DWI for breast lesions in pre-operative MRI can help to obviate unnecessary biopsies by increasing specificity. However, to avoid missing cancers, clinicians should closely monitor lesions located in the same quadrant or lesions ≥1 cm. • DWI can be used to further differentiate lesions during pre-operative cancer staging. • ADC cut-off values were similar in the development and validation cohorts. • DWI improves both PPV and NPV in cases of multicentric lesions. • DWI improves both PPV and NPV in lesions <1 in diameter. • NPVs are decreased in multifocal lesions and lesions ≥1 cm in diameter.

MAMMOGRAPHY AND MAMMOSCINTIGRAPHY WITH 99M TC-MIBI IN THE DIAGNOSIS OF MULTICENTRIC BREAST CANCER

Objective: To compare diagnostic capability of mammography and mammoscintigraphy with 99mTc-methoxyisobutylisonitrile (MIBI) in diagnostic of multicentric breast cancer. Material and Methods: We respectively analyzed 437 consecutive women with suspected breast cancer between 2014 to 2016. All of them underwent mammography and mammoscintigraphy. Craniocaudal and mediolateral oblique images were obtained. Mammoscintigraphy was performed 15-20 min. after intravenous injection 740 MBq of 99mTc-methoxyisobutylisonitrile (MIBI). Final interpretation of the data was done according to histological examination. Results: Breast cancer was detect in 367(84%) of patients. Most of them 320(87%) had single node breast cancer and 47(13%) - multicentric breast cancer. Sensitivity, specificity and accuracy in diagnostic of multicentric breast cancer were 40,4%, 95,3%, 88% for mammography and 83%, 98%, 96% for mammoscintigraphy respectively. The combination of these methods allowed significantly increase sensitivity of breast cancer detection up to 93,6%. Specificity was 93,4%.

A retrospective study on multifocal and multicentric vs. unifocal breast cancer. Preliminary results

Multifocal (MF) and multicentric (MC) breast cancers have been comprehensively studied, but they still remain a controversial subject for many senologists in regards to the best treatment options. Conservatory approach is reserved preponderantly to unifocal localization of the invasive breast carcinoma while in MF and MC the radically techniques are still the main option. The real impact of MC and MF breast cancers on survival is still unknown, but it is presumed to be worse. MF and MC breast cancers are currently over treated by radical mastectomy (RM). The AMAROS trial and also the Z0011 trial recently demonstrated that less surgery does not necessarily mean less local control or worse survival outcomes. About 450 women that underwent surgery for breast cancers stages I-III were included in this monocentric retrospective study; clinical and pathological data were obtained from the database of the Institute of Oncology ”Prof. Dr. Alexandru Trestioreanu” Bucharest. Our primary objective was to see if there is any difference in disease free survival in early breast cancer patients primary treated by conservative surgery according to unifocal (UF) vs. MF vs. MC feature of the invasive component. Our secondary objectives were to identify if there is any correlation between the conservative or radical type of surgery and other clinical and histologcal characterstics; if there is any differences in survival between UF vs. MF vs. MC breast carcinoma. Median follow-up was of 51 months. MC and MF cancers were present in 38 patients (8.4%) and 13 (2.9%) respectively and most of them were treated with mastectomy (6 MF and 19 MC) rather than with breast conservative surgery (BCS). In the entire data analyzed there was no statistical difference between event free survival (EFS) in the subgroup that underwent BCS vs. radical surgery (RS): 21 events (16.4%) vs. 53 events (16.61% ) (p=0.957), median EFS 99.79 mo 95% CI [92.67-106.91] mo vs. 98.19 95% CI [92.81-103.56] mo (p=0.773). We found a significant correlation between recurrence and a family history of cancer (p=0.035), the tumor/node/metastasis (p<0.001), type of surgery (p= 0.035). Relapse rate wasn’t significantly different whatever the type of surgery done. Median EFS wasn’t different between patients that underwent BCS and those that underwent RS. BCS is a reasonable option in selected UF/MC/MF cancers, particularly in younger women with small breast tumors.

P159 - Lobar surgery to facilitate radiotherapy for breast conservation treatment in multifocal and multicentric breast cancers

P159 - Lobar surgery to facilitate radiotherapy for breast conservation treatment in multifocal and multicentric breast cancers

P138 - Does changing classification for multifocal and multicentric breast cancers alter breast conservation rates?

P138 - Does changing classification for multifocal and multicentric breast cancers alter breast conservation rates?

Abstract P1-10-13: Can the risk of radiation-induced cardiac disease in breast cancer be mitigated with cardiac-sparing techniques?

Abstract Introduction: Data suggest that long-term survivors of breast cancer treated with radiation therapy (RT) have an increased risk of cardiac events despite an overall survival benefit, particularly women with left-sided breast cancers. We hypothesized that with cardiac-sparing radiation techniques there would be no difference in long-term cardiac risks between women with right- and left-sided breast cancers. Materials and Methods: The outcomes of 775 consecutive women treated between 1984 and 1999 with breast-conserving therapy (BCT) (n=424) and post-mastectomy radiation therapy (PMRT) (n=351) for stage 0-3 breast cancer were assessed retrospectively through a review of medical records and contact with living patients. The choice of BCT vs PMRT was based on tumor board disposition and patient preference; mastectomy was recommended for multicentric or T3 breast cancers. Ninety-six percent of all node-positive patients received treatment to all nodal regions, including the internal mammary (IM), axillary (AX), and supraclavicular (SC) nodes. BCT patients had computed tomography-planned tangential breast radiation with photons with IM nodes treated within the tangent fields or with a separate en face electron field to minimize cardiac exposure. PMRT patients were treated with en face electron fields for the chest wall and IM for sparing of the lung and heart. The AX and SC nodes were treated with a matched anterior photon field with a posterior-anterior boost field (PAB) when necessary to achieve adequate dose in the AX with both BCT and PMRT. Overall, 411 patients were node-negative and 353 were node-positive. All patients have a minimum potential follow-up of 16.4 years; median actual follow-up for the BCT group was 15 years (range, 0.1-31.2) and for the PMRT group it was 9.5 years (range, 0.1-30.5). Results: Overall survival (OS), cause-specific survival (CSS), and freedom from local-regional recurrence (FFLR) rates for the cohort at 15 years were 58.2%, 72.0%, and 90.8%, respectively. Rates of freedom from cardiac events (FFCE), pulmonary events, and second malignancy were 87.6%, 93.6%, and 86.3%, respectively. On multivariate analysis, OS was correlated with stage (p=.045), number of positive nodes (p=.002), age (p&amp;lt;.0001), diabetes (p =.0021), and modality (p=.0017). Not surprisingly, 15-year survival for patients treated with BCT was better than for patients treated with PMRT (70.9% vs 59.7%; p&amp;lt;.0001). CSS was associated with stage (p=.0207), number of positive nodes (p=.0409), and modality (p=.0003). FFLR was associated with number of positive nodes (p=.0484). FFCE was associated with pretreatment cardiac disease (p&amp;lt;.0001), stage (p=.0461), and age (p=.0056), but not with either breast cancer laterality (p=.1906) or modality (BCT vs PMRT; p=.7487). Discussion: Long-term disease control and survival outcomes were better in BCT than PMRT patients, likely due to selection criteria. Cardiac events were associated with pretreatment heart disease, older age, and stage, suggesting that this population may benefit from advanced radiation techniques that can further limit cardiac dose. Neither breast cancer laterality nor treatment modality was associated with cardiac events. Citation Format: Smith TL, Mokhtech M, Bradley JA, Lightsey JL, Morris CG, Mendenhall NP. Can the risk of radiation-induced cardiac disease in breast cancer be mitigated with cardiac-sparing techniques? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-13.

Model observer design for multi-signal detection in the presence of anatomical noise

As psychophysical studies are resource-intensive to conduct, model observers are commonly used to assess and optimize medical imaging quality. Model observers are typically designed to detect at most one signal. However, in clinical practice, there may be multiple abnormalities in a single image set (e.g. multifocal multicentric (MFMC) breast cancer), which can impact treatment planning. Prevalence of signals can be different across anatomical regions, and human observers do not know the number or location of signals a priori. As new imaging techniques have the potential to improve multiple-signal detection (e.g. digital breast tomosynthesis may be more effective for diagnosis of MFMC than mammography), image quality assessment approaches addressing such tasks are needed. In this study, we present a model observer to detect multiple signals in an image dataset. A novel implementation of partial least squares (PLS) was developed to estimate different sets of efficient channels directly from the images. The PLS channels are adaptive to the characteristics of signals and the background, and they capture the interactions among signal locations. Corresponding linear decision templates are employed to generate both image-level and location-specific scores on the presence of signals. Our results show that: (1) the model observer can achieve high performance with a reasonably small number of channels; (2) the model observer with PLS channels outperforms that with benchmark modified Laguerre–Gauss channels, especially when realistic signal shapes and complex background statistics are involved; (3) the tasks of clinical interest, and other constraints such as sample size would alter the optimal design of the model observer.

Management of Multifocal-Multicentric Breast Cancer: Current Perspective.

The incidence of multifocal (MF) and multicentric (MC) breast cancer has a wide variation among different clinical studies, mostly due to the lack of a standardized classification and definition of these two separate entities. The optimal surgical treatment for multiple ipsilateral breast cancer remains a long debated subject. Multifocal and multicentric breast cancer is usually considered a relative contraindication for breast conserving therapy (BCT). In this narrative review we analyzed differences between MC and MF early breast cancer, the role of magnetic resonance imaging (MRI) in detection of multiple breast lesions, and its role in the surgical approach. We evaluate data from the literature about feasibility of breast conservative surgery and loco-regional treatment modalities. Recent studies brought evidence that treatment of patients with MC/MF breast cancer with BCT plus radiotherapy and adjuvant systemic therapy can have low-rates for in-breast recurrence. Prospective studies are needed to confirm these findings.