Synchronous Bilateral Breast Cancer Research Articles

Abstract PO4-08-04: Comparison of Outcomes and Prognosis between BRCA Pathogenic Variant Carriers Undergoing Breast-Conserving Surgery versus Mastectomy for Breast Cancer

Abstract Introduction: While outcomes are similar following breast-conserving surgery (BCS) or mastectomy among patients with sporadic breast cancer, data are still controversial for germline BRCA pathogenic variant carriers. We previously compared outcome following BCS between BRCA pathogenic variant carriers and non-carriers, and reported higher ipsilateral breast recurrence and comparable prognosis in the carriers. The purpose of this current study was to compare outcomes among BRCA pathogenic variant carriers undergoing BCS versus mastectomy in long-term follow-up period. Methods: Women with a BRCA pathogenic variant and a stage 0-III breast cancer who underwent definitive surgery from 1987–2021 were retrospectively identified from institutional database. Factors including clinicopathologic information and treatment characteristics were identified. Subsequent local recurrence, regional recurrence, distant recurrence, contralateral breast cancer (CBC), breast cancer-specific survival (BCSS), and overall survival (OS) rates were compared between BCS and mastectomy using Kaplan-Meier method and log-rank test. The chi-square test and t-test were used to compare patient characteristics between the two groups. Results: A total of 232 BRCA mutation carriers with 257 cancers including 25 patients with synchronous bilateral breast cancer were identified. Surgical treatment included BCS for 82 cancers and mastectomy for 175 cancers including nipple-sparing mastectomy for 51 cancers. Patient age at surgery and cancer stage did not statistically differ between BCS and mastectomy groups. Comparing to patients choosing mastectomy, patients who underwent BCS were less likely to be aware of their genetic status before surgery and were more likely to receive radiation therapy (p < 0.001). Contralateral risk reducing mastectomy was performed in 22.5% (18/80) in the BCS group and 48.7% (74/152) in the mastectomy group (p < 0.001) concurrently or at any time after the first definitive surgery. Risk reducing salpingo-oophorectomy was performed in 40% (32/80) in the BCS group and 49% (75/152) in the mastectomy group (p = 0.17). At 7.5 years median follow-up, local recurrence rate was statistically higher in the BCS group than in the mastectomy group (20.0% in BSC vs. 4.6% in mastectomy, p = 0.043). In patients who underwent nipple-sparing mastectomy, 4.0% (2/51) had local subcutaneous recurrence and no nipple-areolar recurrence was observed. Median duration from the first definitive surgery to ipsilateral local recurrence was 10.0 years in the BCS group and 2.3 years in the mastectomy group. Regional lymph node recurrence (11.2% in BCS vs. 6.4% in mastectomy, p = 0.62), distant recurrence (13.7% vs. 9.2%, p = 0.84), CBC (15.0% vs. 8.6%, p = 0.70), BCSS (88.8% vs. 94.1%, p = 0.65) and OS (87.5% vs. 94.1%, p = 0.49) rates did not statistically differ between two groups. Conclusions: With 7.5 years median follow-up, higher local recurrence rate was observed in BCS than in mastectomy among BRCA pathogenic variant carriers. Our results found no statistical difference between BCS and mastectomy in regional recurrence, distant recurrence, CBC, and prognosis, indicating relatively higher risk in BCS. While BCS could be an option for BRCA pathogenic variant carriers willing to continue high-risk breast surveillance, shared decision making should be carefully performed based on the long-term local recurrence risk. Citation Format: Kumiko Kida, Junko Takei, Misato Suzuki, Megumi Okawa, Sakurako Kazama, Sakiko Kondo, Michiko Yamanaka, Atsushi Yoshida. Comparison of Outcomes and Prognosis between BRCA Pathogenic Variant Carriers Undergoing Breast-Conserving Surgery versus Mastectomy for Breast Cancer [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 PO4-08-04.

Tomotherapy in synchronous and metachronous bilateral breast cancer: Clinical experience.

The objective of this research is to present our firsthand experience and provide up-to-date data for the further study of cases involving simultaneous breast irradiation using helical Tomotherapy, ©Accuray Inc. The radical treatment options for bilateral breast cancer are surgery, chemotherapy, and radiation therapy. Being that radiotherapy for bilateral breast cancer is challenging due to limitations in the geometry of modern radiotherapy equipment, helical Tomotherapy was chosen as an appropriate technique of irradiation. The retrospective review focused on the records of patients who underwent bilateral irradiation of the breast or chest wall and regional lymph nodes using helical Tomotherapy. Only four patients with bilateral breast cancer completed a radiation therapy course in our center from 2018 to 2023. Two patients underwent radical mastectomy with lymph node dissection on both sides before irradiation. For the other two patients, radical mastectomy was done after neoadjuvant chemotherapy. Acute radiation toxicity scoring was based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Only mild adverse effects, such as general weakness and slight skin irritation below Grade 3, were observed, with no instances of skin swelling, dryness, or pigmentation noted. Evaluation of late complications revealed tissue fibrosis in the area of the internal mammary nodes and respiratory failure with various severity. Complications and deterioration in the cardiovascular system were not observed during the follow-up period, which varied from 3 to 48months. Our results show the efficacy of using helical Tomotherapy considering positive outcomes, being that three out of four patients are in remission with low acute toxicity and late complications. There are a small number of articles describing bilateral breast cancer treatment with helical Tomotherapy. On this occasion, our data could contribute to the studies of tolerant doses for organs at risk and improve the parameters of treatment plans for bilateral breast cancer. Since the small sample of patients with bilateral breast cancer limits the study, a larger cohort of patients is essential to obtain statistically reliable results.

TP53-associated early breast cancer: new observations from a large cohort.

A large well-annotated recent international cohort of Li-Fraumeni (LFS) patients with early-stage breast cancer (BC) was examined for shared features. This multicentre cohort study included females with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic BC diagnosed between 2002-2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were utilized to summarize proportions and differences were assessed by Chi square or Wilcoxon rank sum tests. Metachronous contralateral breast cancer (CBC) risk, radiation-induced sarcoma risk, and recurrence-free survival (RFS) were analyzed by Kaplan-Meier methodology. Among 227 females who met study criteria, the median age of first BC diagnosis was 37 years (range 21-71), 11.9% presented with bilateral synchronous BC and 18.1% had ductal carcinoma in situ (DCIS) only. In total, 166 (73.1%) underwent mastectomies including 67 bilateral mastectomies as first BC surgery. Among those with retained breast tissue, CBC rate was 25.3% at 5-years. Among 186 invasive tumors, 72.1% were stages I-II, 48.9% node-negative, and the most common subtypes were HR+/HER2- (40.9%) and HR+/HER2 + (34.4%). At a median follow-up of 69.9 months (IQR 32.6-125.9), invasive HR+/HER2- disease had the highest recurrence risk among the subtypes (5-year RFS 61.1%, p = .0012). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. We observed high rates of DCIS, HR+ and HER2+ breast cancers, with a worse outcome in the HR+/HER2- luminal tumors despite appropriate treatment. Confirmation of these findings in further studies could have implications for BC care in LFS.

Determining the Need for Metastatic Staging in Patients with Bilateral Breast Cancers.

Introduction: Bilateral breast cancers (BBC) diagnosed at an interval apart are uncommon. While metastatic staging guidelines are established in patients with unilateral breast cancer, its role in BBC diagnosed at an interval apart is unclear. We aim to identify the subgroup who would benefit from metastatic staging at contralateral cancer diagnosis. Methods: Eligible patients were divided into three categories: (A) ipsilateral invasive cancer and contralateral ductal carcinoma in situ (DCIS), (B) bilateral invasive cancers and (C) ipsilateral DCIS and contralateral invasive cancer and reviewed retrospectively. We excluded patients with bilateral DCIS, synchronous BBC diagnosed within 6 months from first cancer, patients who were stage IV at first cancer diagnosis and patients with recurrence prior to contralateral cancer. Results: Of 4516 newly diagnosed breast cancer patients, 79 patients were included. Systemic metastasis occurred in 15.6% of patients in Group B. Having nodal positivity of either cancer which were diagnosed ≤30 months apart and nodal positivity of only the contralateral cancer when diagnosed >30 months apart was significantly associated with systemic metastasis (p = 0.0322). Conclusions: Both the nodal status and a 30 months cut-off time interval between the two cancers can be used to identify patients who will benefit from metastatic staging. This finding requires validation in larger studies.

Post burn and bilateral inflammatory breast cancer: Three case reports from one patient

Inflammatory Breast Cancer (IBC) is the most aggressive form of primary breast cancer. IBC has an incidence of approximately 2.5 cases per 100,000 women. Malignant neoplasms arising from burn scars are well-known but rarely encountered. The subject was reviewed in a comprehensive publication that reviewed the literature between 1923 and 2007 and found 412 well-documented cases of squamous cell carcinoma (71%), basal cell carcinoma (12%), melanoma (6%), sarcoma (5%), other neoplasms (4%), squamo-basal cell carcinoma (1%), and squamous cell-melanoma (1%). In 2008, two cases were reported by Losanof, et al. both female, who were diagnosed with advanced breast cancer many years after severe thermal injury to their breasts. Bilateral synchronous or metachronous breast cancer is well-known and documented except for IBC. To our knowledge, our search using Medline and other searches did not reveal any post-burn IBC or bilateral IBC cases reported in the literature that occurred till 2006. There are only 2 cases reported in 2010 and 2016. We report our 3 case reports presented from one patient; who was diagnosed in 2006; a case of post-burn breast cancer, and to our knowledge the first case report of post-burn IBC type and a rare case report of bilateral metachronous IBC.

Radiotherapy Planning in Synchronous Bilateral Breast Cancer Irradiation: A Dosimetric Study

Background: The large radiation field and surrounding normal structures make treatment planning and dose delivery of synchronous bilateral breast cancer (SBBC) much more difficult than it is for unilateral breast cancer. Intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) can produce acceptable normal tissue sparing while improving target dose coverage compared to 3D-CRT. With this context in mind, we carried out a study to examine the dosimetric variations of IMRT and VMAT techniques using a single isocenter for planning cases of SBBC. Patients and methods: Five patients were considered for this study. All the patients had undergone bilateral mastectomy. Dose prescribed was 50 Gy in 25 fractions. VMAT and IMRT plans were created for each patient. All the plans made were mono-isocentric. Dosimetric data of the target and organs at risk (OAR) were compared. Results: There is a trend towards better PTV coverage using VMAT compared to IMRT (V95 IMRT=94.8720, V95 VMAT=95.8740; P=0.316). VMAT plans significantly improved the dose homogeneity as V105% decreased from 2.886% to 0.312% using VMAT plans (P=0.001). IMRT plans showed trend towards higher lung Dmean and V20Gy than VMAT plans. The irradiation dose to the heart was significantly higher in the IMRT plan than VMAT plan, resulting in Dmean of 15.836 Gy vs 13.580 Gy (P=0.026), V25Gy of 16.498% vs 13.832% (P=0.046) and V30 Gy of 9.774% vs 7.022% (P= 0.043). Conclusion: The single isocentric VMAT technique can be performed conveniently in SBBC. It improves target volume coverage with optimal normal tissue sparing. It is a feasible approach while planning synchronous bilateral breast irradiation.

Is Metastatic Staging Needed for All Patients with Synchronous Bilateral Breast Cancers?

Patients with bilateral breast cancers are uncommon and are associated with a poorer prognosis. While metastatic staging guidelines in patients with unilateral cancer were established, the indication of metastatic staging in patients with bilateral breast cancers is unclear. We aimed to determine which patients with synchronous bilateral breast cancers require metastatic staging at diagnosis. This is the first such reported study, to the best of our knowledge. A retrospective review of newly diagnosed synchronous bilateral invasive breast cancer patients at our institution was performed. We excluded patients with malignant phyllodes or no metastatic staging. Patients' demographics and pathological and staging results were analysed to determine the group of bilateral breast cancer patients who required metastatic staging. A total of 92 patients with synchronous bilateral invasive cancers were included. The mean age was 58 years old, and 64.1% had bilateral invasive ductal carcinoma. 23.9% had systemic metastasis. Nodal status was statistically significant for systemic metastasis on staging (p = 0.0081), with only three patients (3.3%) having negative nodal status and positive metastatic staging. These three patients, however, showed symptoms of distant metastasis. 92.3% of patients with negative nodes also had negative metastatic staging. Using negative nodal status as a guide avoided metastatic staging in 40.4% of all patients. Negative nodal status was the most predictive factor for no systemic metastasis on staging in patients with synchronous bilateral invasive breast cancers. Hence, metastatic staging could be reserved for patients with symptoms of systemic metastasis and/or metastatic nodes. This finding could be validated in larger studies.

Synchronous bilateral male breast cancer: A case report and review of literature

Synchronous bilateral male breast cancer: A case report and review of literature

Patient specific quality assurance of volumetric modulated arc therapy of synchronous bilateral breast cancer

Synchronous bilateral breast cancers (SBBC) present a considerable issue in external beam radiotherapy because of large fields size and large target volumes. Mono-isocentric volumetric modulated arc therapy (VMAT) appears as an appropriate irradiation technique for these types of tumors. The aim of this study was to demonstrate the utility of a 3D DVH pretreatment quality assurance program in VMAT of SBBC cases. Twenty SBBC patients who underwent radiation therapy in our department were retrospectively enrolled in this study. Fifteen patients were treated exclusively to the mammary glands. Five patients benefited from a dose boost on the tumor bed (60Gy). Nine patients were irradiated on the supraclavicular nodes (50Gy). This dose was delivered in 25 fractions and integrated boost was used when appropriate. Depending on the complexity of the treatment plans; 2 or 4 arcs VMAT plans were used in a mono-isocentric technique. The patient specific quality assurance (PSQA) was evaluated using COMPASS measured data, COMPASS reconstructed (CR) and COMPASS computed (CC) dose compared to treatment planning system (TPS) dose. Clinical evaluation was based on DVH metrics for target volumes and organ at risks.The maximum average dose deviation between TPS, CC, and CR was below 3%. The paired t-test between TPS, CC, and CR shows a strong agreement (p < 0.001). The 3DVH dose distribution comparison between TPS and COMPASS were also performed with good gamma score for global analysis.COMPASS was successfully evaluated as a 3DVH pretreatment system for SBBC despite the large fields size and complex target volumes. It allows the verification of the plan in 3D patient anatomy and the evaluation of dose discrepancies.

SYNCHRONOUS BILATERAL BREAST CANCER RIGHT HER 2 POSITIVE AND LEFT HER 2 NEGETIVE- A CASE REPORT

Bilateral breast cancers (BBCs) represent 2–11% of breast cancers. The diagnosis of breast cancer at the same time or up to 6 months in both breasts is known as Synchronous bilateral breast cancer (s-BBC).[1,2]In about 15% to 20% of breast cancers, the cancer cells make too much of a growth-promoting protein known as HER2. These cancers, known as HER2-positive breast cancers, tend to grow and spread more aggressively than HER2-negative breast cancers. Targeted drug therapy uses medicines that are directed at (target) proteins on breast cancer cells that help them grow, spread, and live longer. Anti-HER2 therapies (also called as HER2 inhibitors or HER2 targeted therapies) are a class of medicines used to treat all stages of HER2-positive breast cancer and certain HER2-low breast cancers.Trastuzumab is currently used sequentially after completion of anthracycline-based chemotherapy as a single agent or in combination with taxanes. In this case report we present a female 51 year old patient with synchronous bilateral breast cancer Left breast wasHER2 negative cT2N0M0, stage I and Right breast was HER2 positive cT2N2M0 stage Ia, both breast cancers were hormone receptor positive. The patient was administered six cycles of Inj. genexol-PM, Inj. carboplatin, Inj. pertuzumab, Inj. trastuzumab, Inj. Pegasta as NAC, Followed by bilateral radical mastectomy, patient showed a complete tumor reduction with residual node in right breast contrary to left breast which showed partial response. (Left breast ypT1N0 (sn)M0 and right breast ypT0N1aM0).

Evaluation of Cardiac Substructures Dose Sparing in Single and Dual Isocenter RapidArc™ Radiotherapy Planning for Synchronous Bilateral Breast Cancer.

Purpose This study compares the dosimetry and dose sparing of cardiac substructures in single isocenter and dual isocenter RapidArc™ (Varian Medical Systems, Palo Alto, California, United States) radiotherapy planning for synchronous bilateral breast cancer. Methodology Six synchronous bilateral breast cancer (SBBC) patients received adjuvant radiation with the prescribed dose of 40.05 Gy in 15 fractions to the planning target volume (PTV) without local lymph nodal regions. PTVs and organs at risk (OARs), including both lungs, esophagus, spinal cord, heart, and left anterior descending coronary artery (LAD), both atria and ventricles were contoured. Single isocentric RapidArc (SIRA) and dual isocentric RapidArc (DIRA) plans were made for each patient and dosimetric differences between these two techniques were evaluated. Results There was no statistically significant difference in conformity index (CI) values between SIRA and DIRA plans, with 0.9681±0.01and 0.9721±0.01 (p=0.505), respectively. SIRA planning showed superior homogeneity with homogeneity Index (HI) values of 0.0999±0.01 compared to DIRA planning with HIvalues of 0.1640±0.12 (p=0.230). The mean LAD dose of SIRA was valued higher than that of DIRA planning. Lower mean doses were obtained for both lungs in SIRA plans compared to DIRA plans. Meanwhile, doses to the right atrium, left atrium, left ventricle, right ventricle, and esophagus showed no statistical significance between these two techniques, except in the spinal cord. Conclusion Both SIRA and DIRA plans have satisfactory outcomes in sparing OARs. Meanwhile, SIRA techniques have less setup time and overall machine time.

Clinical Outcomes and Setup Reproducibility in Patients Receiving Synchronous Bilateral Breast Radiation in the Prone Position

Standardized radiation therapy (RT) positioning and planning are vital to treat both breasts without excess toxicity in patients with synchronous bilateral breast cancer (SBBC). We studied clinical outcomes and setup reproducibility in patients with SBBC treated in the prone position. This is a retrospective study of patients receiving RT for SBBC from 2012-2022 treated in the prone position. Patient demographics, RT dose and field, toxicity, and outcomes were collected. RT planning used gantry and table shifts to avoid entrance/exit through contralateral breast and organs at risk. RT delivery was standardized, with left breast treated first. After 2014, radiographic films were placed during the first 5 fractions to evaluate field overlap. Consistent overlap required re-simulation or re-planning. Positional shifts during setup were collected for patients receiving bilateral whole breast irradiation (WBI) and bilateral partial breast irradiation (PBI). A total of 45 patients were treated for SBBC. Median age was 67 years. Median follow-up was 28 months. 35 patients were treated with WBI (1 with low axilla on one side) and 5 with PBI. 5 patients were treated with WBI in one breast and PBI in the other. The most common whole breast dose was 40.5Gy, with a simultaneous integrated boost to the lumpectomy cavity to 48Gy. PBI patients were treated with 30Gy (n = 4) or 40.05Gy (n = 1). 8 patients (17.7%) had acute grade 2 and 1 patient (2%) had acute grade 3 dermatitis. This patient was treated WBI bilaterally and was known to have overlap on GaF. Physician and patient accepted higher toxicity for adequate coverage of bilateral upper inner quadrant tumors. Patients with grade > = 2 dermatitis had bilateral WBI (+/- low axilla) except 1. 6 patients had acute dermatitis in the sternal area (5 were WBI and 1 PBI). Only 2 of these patients had overlap on GaF. Of 20 patients with late toxicity follow-up (> 6 months), 5 (25%) had late grade 1-2 dermatitis. 4 (20%) were treated with WBI (+/-low axilla). 1 patient had both a local and distant recurrence. For setup and treatment delivery, couch shifts recorded for patients treated with bilateral WBI (n = 33) and bilateral PBI (n = 5) were minimal. Mean shifts in nearly all dimensions were limited to sub-centimeter or sub-degree changes, with 2D and cone beam CT (CBCT) imaging. Analysis of GaF showed that only 3 patients (10%) had field overlap. A new plan was created for 1 patient to increase the gap between fields, and for the others, patient and physician accepted overlap for adequate coverage. To our knowledge, this is the first study examining clinical outcomes and setup reproducibility in patients treated with SBBC in the prone position. This study indicates the feasibility of prone bilateral breast treatment with minimal shifts and overlap on daily treatments. However, we do see a higher number of acute dermatitis in patients treated with bilateral WBI (vs. PBI) and that overlap was not seen on GaF in all patients who developed sternal dermatitis.

Intensity-Modulated Proton Therapy (IMPT) Offered Advantageous Dosimetry Compared to Volumetric Arc Therapy (VMAT) or Helical Tomotherapy (HT) in Patients with Synchronous Bilateral Breast Cancer

Radiotherapy of synchronous bilateral breast cancer poses some technical challenges with regards to dose coverage and sparing of organs at risk (OAR). In this study, we aimed to evaluate dosimetric characteristics of 3 different techniques, IMPT vs photon (VMAT and HT). We hypothesized that IMPT would result in lower doses to organs at risk, as compared to the other 2 techniques. A total of 10 patients with synchronous bilateral breast cancer who were treated with VMAT at our institution were retrospectively analyzed. Clinical target volume (CTV) included chest wall and regional nodes (supraclavicular fossa and internal mammary chain) and prescription dose was 40.05 Gy in 15 daily fractions. HT and IMPT plans were generated for each patient. Dose-volume statistics, including planning target volume (PTV) coverage and dose to OAR: lungs, heart, thyroid, spinal cord, brachial plexus and esophagus, were compared between modalities using a paired T-test. Mean age of patients was 61 years (43-84). Majority of the patients (80%) were ER+ PR+ and HER2-. 40% of patients underwent breast reconstruction following surgery. All 3 techniques provided adequate target volume distribution and OAR sparing. Compared to VMAT and HT plans, IMPT had better heart and lung sparing effects, resulting in lower mean and V25 Gy heart dose; mean, V20 Gy and V5 Gy lung dose (p<0.0001). There was no significant difference in VMAT and HT plans for mean heart and lung dose. VMAT plans showed significantly lower V25 Gy heart dose on average (p = 0.04). V5 Gy lung dose was slightly lower in HT compared to VMAT plans, approaching statistical significance (p = 0.08). PTV coverage was adequate for all 3 techniques. All techniques fulfilled cord, esophagus, thyroid and brachial plexus constraints. IMPT plans showed significantly better OAR sparing compared to photon techniques. All 3 techniques met OAR constraints, and resulted in adequate target volume coverage. As IMPT is significantly more costly than VMAT or HT techniques, appropriate patient selection is important to deliver treatment in the most resource-effective manner for patients who would derive the most benefit, for example those with young age or existing heart or lung comorbidities.

Discordance of Oncotype DX scores in synchronous bilateral and unilateral multifocal breast cancers.

Oncotype DX, a 21-gene expression profiling test, has become standard of care in the management of estrogen receptor (ER)-positive breast cancer. In multifocal tumors, it is unclear whether testing of the different foci is necessary. We evaluated the concordance of Oncotype DX recurrence scores (RS) between 2 tumor foci in synchronous bilateral or unilateral multifocal tumors and characterized pathological predictors of discordance. We reviewed 713 ER+, HER2- primary invasive breast cancer patients with Oncotype RS and identified 17 bilateral synchronous patients (34 tumors) and 13 unilateral multifocal patients (26 tumors) with available Oncotype RS on all foci. Discordance in Oncotype RS between synchronous tumors was recorded and associations with clinicopathologic features including tumor size, histology, Nottingham histologic grade, progesterone receptor staining, and Ki67 index were analyzed. Bilateral synchronous tumors were present in older patients (median age 59years) and had larger tumor (median size 17mm) and more discordant histology (10/17, 59%) as compared to unilateral multifocal tumors (median age 49years, p < 0.01; median tumor size 12mm, p = 0.01; discordant histology 2/13, 15%, p = 0.03). Oncotype RS were discordant in 47% (8/17) of bilateral and 54% (7/13) of unilateral multifocal tumors. Concordant Oncotype RS was associated with similar histologic grade and Ki67 index in 78% (7/9) of bilateral and 100% (6/6) of multifocal tumors. In contrast, only 25% (2/8) of bilateral (p = 0.06) and 14% (1/7) of unilateral multifocal (p < 0.01) cases with discordant Oncotype RS had concordant histology grades and Ki67 levels. In synchronous tumors with discordant Oncotype RS and Ki67 index, all (4/4) foci with higher RS had higher Ki67 index. Discordance of Oncotype RS is common in both bilateral and unilateral multifocal breast cancer and is likely associated with discordant histologic grade or Ki67.

Comparison of Clinicopathologic Features and Outcomes Between Synchronous and Metachronous Bilateral Breast Cancer

Purpose: Bilateral breast cancer (BBC) can be divided into two concurrent lesions, depending on the time of occurrence of primary cancer and secondary tumors after treatment of the primary cancer. This study aimed to compare the clinicopathological characteristics and results of synchronous BBC (SBBC) and metachronous BBC (MBBC).Methods: Data of patients diagnosed with breast cancer at Wonkwang university Hospital between October 1991 and October 2021 were retrospectively reviewed. Data of 3,259 patients who were diagnosed with malignant neoplasm of the right or left breast were reviewed. The tumor was defined as SBBC when another cancer was identified as BBC simultaneously or within six months after the primary breast cancer, and as MBBC when another cancer was identified after six months. Among patients with BBC, 31 had SBBC and 32 had MBBC.Results: In SBBC patients, the median age was 59.9 years, and the condition was diagnosed 3.3 years later compared with MBBC. The primary and secondary tumors of SBBC had lower disease stage, even when diagnosed late. Except for tumor, node, and metastasis stage, MBBC showed more invasive ductal carcinoma, while SBBC showed relatively more ductal carcinoma &lt;i&gt;in situ&lt;/i&gt; in both primary and secondary tumors compared with MBBC. In addition, SBBC showed lower hormone receptor positivity rates and Ki-67 levels compared with MBBC. MBBC patients showed a higher survival rate compared with SBBC patients. MBBC is associated with higher overall survival rate compared with SBBC, and its prognosis is not worse compared with that of unilateral breast cancer. In the case of secondary tumor that develops in the contralateral breast without evidence of metastasis, the survival rate is similar to that of unilateral breast cancer, while the treatment is similar to that of primary tumor.Conclusion: As those with SBBC have a worse survival, these patients will require more medical attention; meanwhile, MBBC requires an active treatment approach that is equivalent to that for unilateral breast cancer.

Synchronous Bilateral Breast Cancer With Discordant Receptor Status: Treating One Patient but Two Diseases

The expression of hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor-2 (HER2) has been used for both therapeutic and prognostic purposes in the management of breast cancer. The presence of a discordant receptor status complicates the approach to treatment in patients with synchronous bilateral breast cancer. We describe the case of a 45-year-old female with synchronous bilateral breast cancer with a triple-negative tumor and a contralateral HER2-positive tumor and discussed the impact of this on the approach to therapeutic management.

Synchronous Bilateral Breast Cancers Are Distinct Diseases.

Contralateral tumor subtype affects immune infiltration and therapy response in synchronous bilateral breast cancer.

P026 Synchronous and metachronous bilateral breast cancers: explanation of clinical differences in terms of lead-time bias and late detection

P026 Synchronous and metachronous bilateral breast cancers: explanation of clinical differences in terms of lead-time bias and late detection

Effectiveness and tasks of breast MRI surveillance for high-risk women with cancer susceptibility genes other than BRCA1/2: a single institution study.

In Japan, with the introduction of multigene panel testing, there is an urgent need to build a new medical system for hereditary breast cancer patients that covers pathogenic variants other than BRCA1/2. The aim of this study was to reveal the current status of breast MRI surveillance for high-risk breast cancer susceptibility genes other than BRCA1/2 and the characteristics of detected breast cancer. We retrospectively examined 42 breast MRI surveillance with contrast performed on patients with hereditary tumors other than BRCA1/2 pathogenic variants at our hospital from 2017 to 2021. MRI exams were evaluated independently by two radiologists. Final histopathological diagnosis for malignant lesions were obtained from surgical specimen. A total of 16 patients included TP53, CDH1, PALB2, ATM pathogenic variants and 3 variant of unknown significance. 2 patients with TP53 pathogenic variants were detected breast cancer by annual MRI surveillance. The rate of cancer detection was 12.5% (2/16). One patient was detected synchronous bilateral breast cancer and unilateral multiple breast cancers (3 lesions in 1 patient), so there were 4 malignant lesions in total. Surgical pathology of 4 lesions were 2 ductal carcinoma in situ, 1 invasive lobular carcinoma, and 1 invasive ductal carcinoma. MRI findings of 4 malignant lesions were detected as 2 non mass enhancement, 1 focus and 1 small mass. All of 2 patients with PALB2 pathogenic variants had previously developed breast cancer. Germline TP53 and PALB2 were strongly associated with breast cancer, suggesting that MRI surveillance is essential for breast cancer-related hereditary predisposition.

Cardiac dose in the treatment of synchronous bilateral breast cancer patients between three different radiotherapy techniques (VMAT, IMRT, and 3D CRT)

PurposeSynchronous bilateral irradiation of both mammary glands and chest wall is a challenging task due to technical difficulties and limited evidence supporting an optimal technique to improve treatment outcomes. We studied and compared the dosimetry data of three radiotherapy techniques to select the most optimal one.MethodsWe compared three-dimensional conformal radiation treatment (3D CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) during irradiation of synchronous bilateral breast cancer in nine patients followed by examination of dose distribution to the cardiac conduction system (SA node, AV node and Bundle of His), myocardium, lungs, left anterior descending artery (LADA) and right coronary artery (RCA) .ResultsVMAT is the most sparing technique for SBBC treatment. Even though doses to the SA node, AV node and Bundle of His were higher with VMAT (Dmean were 3.75 ± 0.62, 2.58 ± 0.83 and 3.03 ± 1.18 Gy respectively) compared with 3D CRT (Dmean were 2.61 ± 0.66, 1.52 ± 0.38 and 1.88 ± 0.70 Gy respectively), this difference is statistically insignificant. Doses to the right and left lung (average Dmean = 12.65 ± 3.20 Gy, V20Gy = 24.12 ± 6.25%), myocardium (Dmean = 5.33 ± 1.51 Gy, V10Gy = 9.80 ± 3.83%, V20Gy = 7.19 ± 3.15%, V25Gy = 6.20 ± 2.93%), and LADA (Dmean = 10.04 ± 4.92 Gy, V20Gy = 18.17 ± 13.24% and V25Gy = 15.41 ± 12.19%) were highest with 3D CRT. The highest Dmean in the cardiac conduction system (5.30 ± 2.23, 3.15 ± 1.61 and 3.89 ± 1.85 Gy respectively) was observed with IMRT, and a similar effect was noted in RCA (Dmean = 7.48 ± 2.11 Gy).ConclusionVMAT is the optimal and satisfactory radiation therapy technique for sparing organs at risk (OARs). With VMAT, a lower Dmean value was noted in the myocardium, LADA, and lungs. The use of 3D CRT significantly increases the dose of radiation reaching the lungs, myocardium, and LADA, which can subsequently cause cardiovascular and lung complications, but not in the cardiac conduction system.