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Abstract Background Since the FDA approved immune-enhancing therapies for patients with high microsatellite instability (MSI-H) and/or mismatch repair deficiency (dMMR), recognizing these biomarkers in solid tumors has gained clinical importance. Although MSI-H and dMMR are considered uncommon in breast cancer, previous studies on bilateral breast cancer (biBC) identified a surprisingly high frequency of MSI. Methods In this study, we aimed to describe the prevalence of dMMR and its association with clinicopathologic parameters in biBC. We performed immunohistochemistry with anti-MMR proteins on tissue microarrays (TMAs) with 58 bilateral breast cancer cases. The biomarkers used were MLH1, PMS2, MSH2, MSH6, ER, PR, HER2 and Ki67. SPSS was used for data analysis. Results Four (6.9%) cases showed dMMR on TMAs. Three (75%) of the dMMR cases were luminal and one (25%) was triple negative. Two biBC cases presented unilateral dMMR. No association between dMMR status and clinicopathologic parameters was found. Conclusions This work highlights a noticeable frequency of dMMR in bilateral breast cancer and builds upon previous research in this area, suggesting routine MMR protein testing as part of the immunohistochemical panel for biBC to identify candidates for immune-enhancing therapies.

Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.

Purpose of study: 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. Methods: 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. Results: 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 48 months. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Bilateral breast cancer (BBC), an infrequent breast cancer subtype, has primarily been studied in terms of incidence, prognosis, and through comparative analysis of synchronous (SBBC) and metachronous (MBBC) manifestations. The advent and application of organoid technology hold profound implications for tumor research and clinical management. This study represents the pioneering use of organoid models in BBC research. We established organoid lines from two surgical tumor specimens of a BBC patient, with one line undergoing detailed pathological and genomic analysis. The BBC organoid from the right breast demonstrated a marker expression profile of ER (-), PR (-), HER-2 (0), and Ki67 index 10%, indicating that it may derived from the TNBC tissue. Whole Exome Sequencing (WES) displayed consistent set of Top10 cancer driver genes affected by missense mutations, frameshift mutation, or splice site mutations in three tumor tissues and the organoid samples. The organoids' single nucleotide polymorphisms (SNPs) were more closely aligned with the TNBC tissue than other tumor tissues. Evolutionary analysis suggested that different tumor regions might evolve from a common ancestral layer. In this case, the development of BBC organoids indicated that simultaneous lesions with diverse molecular profiles shared a high degree of consistency in key tumor-driving mutations. These findings suggest the feasibility of generating BBC organoids representing various molecular types, accurately replicating significant markers and driver mutations of the originating tumor. Consequently, organoids serve as a valuable in vitro model for exploring treatment strategies and elucidating the underlying mechanisms of BBC. [ABSTRACT FROM AUTHOR]

We present a complex case of a patient diagnosed with bilateral breast cancer. The patient initially underwent bilateral skin-sparing mastectomy and immediate subpectoral implant-base breast reconstruction. She had an uncomplicated postoperative recovery. However, three months later, she developed a severe and persistent local infection during adjuvant chemotherapy, resulting in the loss of the breast implants and the formation of massive deforming scars in the chest area. To address this, the patient underwent a series of reconstructive procedures. Lipofilling was used on the chest wall to improve skin quality, followed by a late bilateral transverse rectus abdominis myocutaneous flap for breast reconstruction. Additionally, the final aesthetic result was enhanced by applying a 3-D tattoo. This case highlights the use of a sequence of reconstructive procedures as a feasible alternative to manage complex and extensive scars after failure of primary breast reconstruction. [ABSTRACT FROM AUTHOR]

Bilateral breast cancer in males is an exceedingly rare diagnosis. In this case report, we will discuss the ultrafast sequence findings of a bilateral male breast cancer with different subtypes on his staging dynamic contrast enhanced (DCE) MRI with ultrafast technique. A 94-year-old male presented with bilateral palpable complaints in his breasts. Diagnostic mammography and ultrasound images demonstrated bilateral irregular masses with nipple retraction. Biopsies were performed and the histopathologic examination revealed invasive breast carcinoma of no special type in 1 breast and invasive micropapillary carcinoma in the other breast. Staging MRI with ultrafast sequence showed significant enhancement differences between 2 different subtypes, correlating with the different levels of tumor aggressiveness. Different ultrafast metrics, such as time-to-enhancement and maximum slope, may help to differentiate between several subtypes of breast cancer and serve as prognostic indicators. This case report discusses the application of ultrafast sequence in predicting breast cancer subtypes in a male patient with bilateral disease.

Breast reconstruction has, largely, abated the agony associated with mastectomy following a breast cancer diagnosis. The categorization of the reconstruction method exists based on the time of reconstruction and the use of substance for the reconstruction. Presumably, immediate and delayed breast reconstructions, based on the time of reconstruction, have their individual merits and demerits, and each of them leverages upon the other for a particular aspect. However, simultaneous use of both the time-based methodologies is unusual. The title however paradoxical reflects the upcoming trends in breast reconstruction. These can be attributed to integrated approach between the breast oncosurgeons and plastic surgeons and to the improved awareness about the malignancy, various possible reconstructive measures and increased life span of human beings. [ABSTRACT FROM AUTHOR]

Background: Bilateral breast cancer (BC) has an incidence of 1 to 3 %. This study aimed to describe the clinicopathologic characteristics and management of bilateral BC, estimate disease-free survival (DFS), and compare DFS with unilateral BC. Methods: A retrospective analysis was performed for patients who had bilateral invasive BC or unilateral invasive BC and contralateral ductal carcinoma in situ (DCIS) treated at Mayo Clinic Rochester from 2008 to 2022. A 4:1 matched cohort of patients with unilateral invasive BC was used for comparison. The groups were compared using Wilcoxon rank-sum or chi-square tests. Disease-free survival was analyzed using the Kaplan-Meier method and log-rank test, with Cox proportional hazards regression used for multivariable analysis. Results: The study identified 278 cases of bilateral breast cancer (177 cases of bilateral invasive cancer and 101 cases of unilateral invasive cancer with contralateral DCIS), representing 4.1 % of invasive BCs. Biologic subtype was concordant between sides in 79.8 % of the patients. Initial surgery was bilateral mastectomy for 76.6 %, bilateral lumpectomy for 20.5 %, and unilateral mastectomy with unilateral lumpectomy for 2.9 % of the patients. Pathogenic variants in breast cancer predisposition genes were present in 21.7 % of those tested. The patients who had bilateral BC presented with a higher cT category than the patients who had unilateral BC (p = 0.02), and a higher proportion presented with ILC (17.3 % vs 10.9 %; p = 0.004), estrogen receptor-positive (ER+) disease (89.2 % vs 84.2 %; p = 0.04), multicentric/multifocal disease (37.1 % vs 24.3 %; p < 0.001), breast cancer pathogenic variant (21.7 % vs 12.4 %; p = 0.02), and palpable presentation (48.2 % vs 40.8 %; p = 0.03). The patients with bilateral BC showed DFS similar to that for the unilateral BC cohort (p = 0.71). Conclusions: Bilateral BCs most commonly are biologically concordant between sides. Bilateral BC presented more commonly with larger tumors, lobular histology, ER+ status, multicentricity or multifocality, pathogenic variant, and palpable disease. Bilateral BC is not associated with worse DFS than unilateral BC. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: Bilateral synchronous tumors were present in older patients (median age 59 years) and had larger tumor (median size 17 mm) and more discordant histology (10/17, 59%) as compared to unilateral multifocal tumors (median age 49 years, p < 0.01; median tumor size 12 mm, 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. Conclusion: Discordance of Oncotype RS is common in both bilateral and unilateral multifocal breast cancer and is likely associated with discordant histologic grade or Ki67. [ABSTRACT FROM AUTHOR]

Background: The incidence of multiple malignant primary tumors (MMPT) is increasing which needs attention. Hence, we undertook this study to analyze clinico-demographic details and treatment outcomes in patients with non-head and neck MMPT. Materials and Methods: Hospital case records of patients with histopathology proven MMPT registered in the radiation oncology department from January 1, 2008 to December 31, 2020 were retrospectively studied. Modified Warren–Gates criteria were used to define MMPT. Patients with MMPT of the head and neck (both an index and second primary as head–neck) were excluded from the study. Demographic and clinical details were recorded and analyzed. Results: Forty-two eligible cases of non-head and neck MMPT were studied. The median age at diagnosis of an index case was 55 years (minimum 21, maximum 85) with a male to a female sex ratio of 5:37. Twelve patients had synchronous (28.57%) and 30 had metachronous (71.42%) MMPT. The average period between metachronous tumors was 77.77 months (minimum 12, maximum 312). The most common site of an index and second primary tumor was the breast (26; 61.90% and 23; 54.76%, respectively). Seventeen (65.38%) out of 26 index breast cancer were bilateral breast cancer and nine were others. In six cases of MMPT, there was an association between the breast and cervix. Conclusion: Breast cancer was the most common site for both an index and second primary malignancy followed by genital cancers. With cautious monitoring and patient education, second primary tumor could be detected earlier and managed better giving a good quality of life to patients. [ABSTRACT FROM AUTHOR]

Background: The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known. Methods: Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer. Results: The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138). Conclusions: Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations. [ABSTRACT FROM AUTHOR]

Background: The incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC. Case reports: Five patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up. Conclusion: Our findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC. [ABSTRACT FROM AUTHOR]

BackgroundRetroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using 18F-FDG PET/CT, providing help for clinical diagnosis and treatment.Case reportA 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal 18F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal 18F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant 18F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction.ConclusionIn this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.

There is paucity of literature regarding the demography, histopathology, management, and outcomes of bilateral breast cancer (BBC). We present our experience of treating 127 BBC with multimodality management. An audit of prospectively maintained computerized breast cancer database of the department of surgical oncology at a tertiary care center was performed. Demography, clinical profile, molecular sub-types, treatment patterns, and outcomes were analyzed. A total 127 patients presented with BBC between 1992 and 2019. Ninety-four had metachronous (MBBC) and 33 had synchronous breast cancer (SBBC). Most contralateral breast cancer (CBC) patients had early-stage breast cancer in comparison to the index side cancer (37% vs 32%). Ninety-four patients underwent bilateral mastectomy and only 18 patients underwent bilateral breast conservation. Seventy-one patients undergoing BCS and surgery for LABC were given postoperative radiotherapy. All patients received adjuvant chemo- and/or hormonal therapy both for index and CBC based on the stage and hormone receptor status. Thirty-three percent of patients had either locoregional or distant relapse. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) of the entire cohort were 86.6% and 68.4% respectively. There was no difference in the OS and DFS between SBBC and MBBC. The incidence of BBC is expected to increase with effective diagnostic and therapeutic interventions and improving survival. Patients require individualized treatment planning in a multidisciplinary treatment setting. [ABSTRACT FROM AUTHOR]

BackgroundThe incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC.Case reportsFive patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up.ConclusionOur findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC.

Introduction: The purpose of this study was to compare the dosimetric parameters of volumetric modulated arc therapy (VMAT) treatment plans using coplanar and noncoplanar beams in patients with bilateral breast cancer/s (BBCs) in terms of organ at risk sparing and target volume coverage. The hypothesis was to test whether VMAT with noncoplanar beams can result in lesser dose delivery to critical organs such as heart and lung, which will result in lesser overall toxicity. Materials and Methods: Data of nine BBC cases treated at our hospital were retrieved. Computed tomography simulation data of these cases was used to generate noncoplanar VMAT plans and the parameters were compared with standard VMAT coplanar plans. Contouring was done using radiation therapy oncology group guidelines. Forty-five Gray in 25 fractions was planned followed by 10 Gy in five fractions boost in breast conservation cases. Results: No significant difference in planning target volume (PTV) coverage was found for the right breast/chestwall (P = 0.940), left breast/chestwall (P = 0.872), and in the total PTV (P = 0.929). Noncoplanar beams resulted in better cardiac sparing in terms of Dmean heart. The difference in mean dose was >1 Gy (8.80 ± 0.28 - 7.28 ± 0.33, P < 0.001). The Dmean, V20 and V30 values for total lung slightly favor noncoplanar beams, although there was no statistically significant difference. The average monitor units (MUs) were similar for coplanar plans (1515 MU) and noncoplanar plans (1455 MU), but the overall treatment time was higher in noncoplanar plans due to more complex setup and beam arrangement. For noncoplanar VMAT plans, the mean conformity index was slightly better although the homogeneity indices were similar. Conclusion: VMAT plans with noncoplanar beam arrangements had significant dosimetric advantages in terms of sparing of critical organs, that is Dmean of heart doses with almost equivalent lung doses and equally good target coverage. Larger studies with clinical implications need to be considered to validate this data. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to compare the dosimetric parameters of volumetric modulated arc therapy (VMAT) treatment plans using coplanar and noncoplanar beams in patients with bilateral breast cancer/s (BBCs) in terms of organ at risk sparing and target volume coverage. The hypothesis was to test whether VMAT with noncoplanar beams can result in lesser dose delivery to critical organs such as heart and lung, which will result in lesser overall toxicity. Materials and Methods: Data of nine BBC cases treated at our hospital were retrieved. Computed tomography simulation data of these cases was used to generate noncoplanar VMAT plans and the parameters were compared with standard VMAT coplanar plans. Contouring was done using radiation therapy oncology group guidelines. Forty-five Gray in 25 fractions was planned followed by 10 Gy in five fractions boost in breast conservation cases. Results: No significant difference in planning target volume (PTV) coverage was found for the right breast/chestwall (P = 0.940), left breast/chestwall (P = 0.872), and in the total PTV (P = 0.929). Noncoplanar beams resulted in better cardiac sparing in terms of Dmean heart. The difference in mean dose was >1 Gy (8.80 ± 0.28 − 7.28 ± 0.33, P < 0.001). The Dmean, V20 and V30 values for total lung slightly favor noncoplanar beams, although there was no statistically significant difference. The average monitor units (MUs) were similar for coplanar plans (1515 MU) and noncoplanar plans (1455 MU), but the overall treatment time was higher in noncoplanar plans due to more complex setup and beam arrangement. For noncoplanar VMAT plans, the mean conformity index was slightly better although the homogeneity indices were similar. Conclusion: VMAT plans with noncoplanar beam arrangements had significant dosimetric advantages in terms of sparing of critical organs, that is Dmean of heart doses with almost equivalent lung doses and equally good target coverage. Larger studies with clinical implications need to be considered to validate this data.

Abstract Background Bilateral breast cancer (BBC), as well as ovarian cancer, are significantly associated with germline deleterious variants in BRCA1/2, while BRCA1/2 germline deleterious variants carriers can exquisitely benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. However, formal genetic testing could not be carried out for all patients due to extensive use of healthcare resources, which in turn results in high medical costs. To date, existing BRCA1/2 deleterious variants prediction models have been developed in women of European or other descent who are quite genetically different from Asian population. Therefore, there is an urgent clinical need for tools to predict the frequency of BRCA1/2 deleterious variants in Asian BBC patients balancing the increased demand for and cost of cancer genetics services. Methods The entire coding region of BRCA1/2 was screened for the presence of germline deleterious variants by the next generation sequencing in 123 Chinese BBC patients. Chi-square test, univariate and multivariate logistic regression were used to assess the relationship between BRCA1/2 germline deleterious variants and clinicopathological characteristics. The R software was utilized to develop artificial neural network (ANN) and nomogram modeling for BRCA1/2 germline deleterious variants prediction. Results Among 123 BBC patients, we identified a total of 20 deleterious variants in BRCA1 (8; 6.5%) and BRCA2 (12; 9.8%). c.5485del in BRCA1 is novel frameshift deleterious variant. Deleterious variants carriers were younger at first diagnosis (P = 0.0003), with longer interval between two tumors (P = 0.015), at least one medullary carcinoma (P = 0.001), and more likely to be hormone receptor negative (P = 0.006) and HER2 negative (P = 0.001). Area under the receiver operating characteristic curve was 0.903 in ANN and 0.828 in nomogram modeling individually (P = 0.02). Conclusion This study shows the spectrum of the BRCA1/2 germline deleterious variants in Chinese BBC patients and indicates that the ANN can accurately predict BRCA deleterious variants than conventional statistical linear approach, which confirms the BRCA1/2 deleterious variants carriers at the lowest costs without adding any additional examinations.

The incidence of synchronous or metachronous bilateral breast cancer (SBBC vs. MBBC) has been reported to range from 1.4 to 11.8%. BRCA1/2 deleterious mutation is a significant risk factor for developing synchronous or metachronous bilateral breast cancer. We aimed to examine the clinical and pathological results of patients who developed synchronous or metachronous bilateral breast cancer and to whom we applied BRCA1/2 tests. The files of 1420 patients with breast cancer were analyzed. Among 33 breast cancer patients who underwent the BRCA1/2 gene test, 16 synchronous and 17 metachronous bilateral breast cancer patients were included. Demographics, family history, preoperative diagnosis, tumor properties, histopathological results, immunohistochemistry, multicentrity, stages, metastasis status, mastectomy applications, local and axillary recurrence status, neoadjuvant chemotherapy (NCT), adjuvant therapy age at the first and second tumor, the time elapsed between the development of two tumors, the differences between the synchronous or metachronous tumors, BRCA testing results, overall survival, and disease-free survival were analyzed retrospectively. BRCA 1/2 gene was positive in 8/16 SBBC and 8/17 MBBC. Ten patients were identified as BRCA1 + and six patients as BRCA2 +. BRCA1/2 + two patients and BRCA1/2- two patients died due to metastatic disease. Survival time did not differ significantly between SBBC and MBBC groups (p = 0.153). The survival curves of the patients with or without the BRCA1/2 deleterious mutation did not differ significantly, and the BRCA1/2 variant did not significantly affect survival (p = 0.957). Patients with synchronous or metachronous bilateral breast cancer are likely to be carriers of the BRCA1/2 deleterious mutation. If the BRCA1/2 mutation is investigated and detected in suitable patients, effective methods can be developed to screen other cancer types that may occur alongside breast cancer in these patients, and morbidity and mortality rates can be reduced. [ABSTRACT FROM AUTHOR]

BACKGROUND: Breast cancer (BC) and obesity are two closely associated pathologies with increasing incidence and mortality rates. Bilateral Breast Cancer (BBC) displays a low incidence rate within BC and obesity represents a major risk factor. OBJECTIVE: The aim of this study is to analyzed BBC clinicopathological features distribution and determine the potential influence of obesity in BBC in these same features and overall survival. METHODS: Clinicopathological information was obtained from 42 cases of women with BBC diagnosed in IPO-Porto. To evaluate the frequency distribution of the clinicopathological data, a chi-square goodness of fit test was performed for BBC cases. A chi-square test of independence was applied for BMI stratification. Cox regression was performed for overall survival. Statistical significance was set at p-value < 0.05. RESULTS: Distribution of BBC clinicopathological features was found to be statistically significant in family history (p-value < 0.001), BBC type (p-value < 0.001), stage (p-value = 0.005), differentiation grade (p-value < 0.001), receptor expression (p-value < 0.001) and histological type (p-value = 0.031). In comparison to the statistical expected results, we observed an increased cases of absence of family history and less cases of metachronous BBC. Histological types between tumours of BBC were mostly concordant. All cases presented concordant receptor expression. Analysis stratified by BMI revealed that obese women were diagnosed later, although without statistical significance. All obese women presented poor differentiation grade (n = 6). Overweight patients display a tendency to a better overall survival with lower tumour stages and lower differentiation grades. CONCLUSIONS: Our results reveal the same receptor expression between contralateral tumours. Also, most tumours share the same histological type. When stratified by BMI, we observed a tendency for overweight women to have improved overall survival. [ABSTRACT FROM AUTHOR]

Purpose: This study compares photon and proton therapy plans for patients with synchronous bilateral early breast cancer and estimates risks of early and late radiation-induced toxicities. Materials and Methods: Twenty-four patients with synchronous bilateral early breast cancer receiving adjuvant radiation therapy using photons, 3-dimensional conformal radiation therapy or volumetric modulated arc therapy, were included and competing pencil beam scanning proton therapy plans were created. Risks of dermatitis, pneumonitis, acute esophageal toxicity, lung and breast fibrosis, hypothyroidism, secondary lung and esophageal cancer and coronary artery events were estimated using published dose-response relationships and normal tissue complication probability (NTCP) models. Results: The primary clinical target volume V95% and/or nodal clinical target volume V90% were less than 95% in 17 photon therapy plans and none of the proton plans. Median NTCP of radiation dermatitis ≥ grade 2 was 18.3% (range, 5.4-41.7) with photon therapy and 58.4% (range, 31.4-69.7) with proton therapy. Median excess absolute risk (EAR) of secondary lung cancer at age 80 for current and former smokers was 4.8% (range, 0.0-17.0) using photons and 2.7% (range, 0.0–13.6) using protons. Median EAR of coronary event at age 80, assuming all patients have preexisting cardiac risk factors, was 1.0% (range, 0.0–5.6) with photons and 0.2% (range, 0.0–1.3) with protons. Conclusion: Proton therapy plans improved target coverage and reduced risk of coronary artery event and secondary lung cancer while increasing the risk of radiation dermatitis.

Purpose: Volumetric Modulated Arc Therapy (VMAT) exhibits potent advantages regarding target volume coverage and protection of organs at risk, notably in the context of anatomical constraints. Nevertheless, reports concerning VMAT for the treatment of synchronous bilateral breast cancers (SBBC) have been scarce to date. As such, we conducted this observational study to assess efficacy, safety and feasibility of VMAT in SBBC. Materials and Methods: From August 2011 to December 2017, 54 consecutive patients with SBBC with or without axillary nodes involvement underwent a treatment protocol containing radiotherapy using VMAT. A total dose (TD) of 52.2Gy in 29 fractions was delivered to breast and internal mammary chain (IMC) nodes Planning Target Volume (PTV) plus, if applicable, a TD of 49.3Gy in 29 fractions to the supra- and infra-clavicular nodes PTV and a TD of 63.22Gy in 29 fractions to tumor boost PTV. Lungs, heart, esophagus, trachea, liver, thyroid and spinal cord were considered as organs at risk. VMAT feasibility and organ at risk sparing were evaluated by treatments planning of the 20 first enrolled patients. Tolerance and patients' outcome were prospectively monitored by acute/late toxicities records and by the analysis of overall survival (OS), locoregional recurrence-free survival (LRFS) and recurrencefree survival (RFS). Results: Breast, supraclavicular nodes and boost PTV coverage was adequate with at least 98% of PTV encompassed by more than 95% of the prescribed dose. Less than 90% of IMC PTV was encompassed by 95% of the prescribed dose. Mean lung dose was 12.3Gy (range: 7.7 - 18.7); mean heart dose was 10.7Gy (range: 6.2 - 22.3). Concerning acute toxicities, only 2 patients experienced grade 3 skin toxicity (3.7%) and only 1 patient developed grade 1 pneumonitis. After a median follow-up of 5.3 years, grade 2 fibrosis and/or shrinking was observed in 5 patients (10%), and grade 3 fibrosis in 1 patients (2%). The 5-year LRFS-rate, RFS-rate and OS were 98% [95% CI= 86.12-99.70%], 96% [95% CI= 84.63-98.96%] and 100%, respectively. [ABSTRACT FROM AUTHOR]

Objectives. The purpose of this study was to assess and compare the clinicopathological, molecular pathology, treatment and survival characteristics in patients with metachronous bilateral breast cancer (mBBC) and synchronous breast cancer (sBBC) Materials and methods. A cohort of 658 patients with breast cancer treated at the Coltea Clinical Hospital, Surgery Department, between January 2015 and December 2019 and followed-up until August 2020 was studied. Data pertaining to patients who were diagnosed as having bilateral breast cancer were retrospectively reviewed and collected. A 3-months interval was used to distinguish metachronous from synchronous tumors. Among patients with bilateral breast cancer, assessment parameters included patient characteristics, histological and molecular pathology features and the performed treatment that were statistically evaluated comparing the first and second tumor of each group and among groups. Survival analysis was performed comparing mBBC and sBBC patients. SPSS was used for data analysis. Outcomes. Of the 658 patients with primary breast cancer, 35 (5.3%) patients were diagnosed as having bilateral breast cancer (25 (3.8%) mBBC and 10 (1.5%) sBBC). When clinical and histopathological parameters were statistically evaluated, age, menopausal status, tumor size, number of invaded nodes and anatomic stage were found to be significant between the tumors of the metachronous group and tumor size, pathologic T(tumor) and stage between tumors of the synchronous group. Hormonal receptor (HR) status concordance was higher in the synchronous group (85.7%, p = 0.010), with a higher percentage of ER positive (71.4%) and PR positive (71.4%) concordance of the tumors. In terms of survival analysis, there was a difference in overall survival (OS, p = 0.005), disease-free survival (DFS, p = 0.011) and distant relapse-free survival (p = 0.003) between mBBC and sBBC. The mean disease-free survival for patients in whom metachronous tumor occurred within less than 5 years was 63.3 months, for sBBC patients was 39.6 months, whereas for patients with more than 5 years was 437.9 months (p = 0.012, Log Rank). Discordant biomarker defined subgroup (ER,HER2) patients were associated with better disease-free survival (p = 0.047, Log Rank) and better distant relapse-free survival (p = 0.015, Log Rank) in overall patients. In terms of loco-regional relapse-free survival, although mBBC and sBBC patients showed no statistical significant difference earlier in the time course (p = 0.088, Breslow; p = 0.054 Tarone-Ware), among mBBC patients was observed a better outcome (p = 0.027, Log Rank). Conclusions. Based on survival analysis, patients in whom metachronous tumor developed after more than 5 years, had a better distant relapse-free survival. Patients with synchronous bilateral breast cancer were associated with worse disease outcome based on overall survival analysis and disease free-survival rates with more frequent rates of distant metastasis. Outcome of patients in whom metachronous tumor was diagnosed within less than 5 years might be similar to synchronous tumors. Patients with discordant ER,HER2 status showed a better disease outcome. Although concordance in HR status and molecular subtype, did not show statistical significant differences, it is a subject which deserves further clinical observation.

Abstract Bilateral breast cancer (BBC) is an uncommon subset of breast cancer (BC), and it may present as synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). Through this study, we aimed to evaluate the proportion of BBC in BC and compare the clinicopathological characteristics, treatment, and outcomes of sBBC and mBBC at an academic cancer center in China. Patients with BC consecutively treated between 2006 and 2016 were retrospectively reviewed. Patients with BBC were included. In total, 3924 patients with BC were analyzed and 127 patients with BBC (28 sBBC, 99 mBBC) with a median follow‐up of 98 months were identified. The proportion of BBC was 3.2% (0.7%, sBBC; 2.5%, mBBC). The median age at the first diagnosis of mBBC was significantly younger than that at the first diagnosis of sBBC (p = 0.027). Patients diagnosed as having sBBC were more likely to have a positive family history (p = 0.047). The first tumors of mBBC were detected at a significantly earlier tumor stage compared with those of sBBC (p = 0.028). The concordance rates of histopathologic type in the first and second tumors were 60.7% and 58.0% in sBBC and mBBC, respectively. sBBC had a significantly poorer disease‐free survival than mBBC did (p = 0.001). BBC is a rare disease affecting the Chinese population. sBBC is associated with a greater prevalence of a family history of breast cancer and poorer prognosis, compared with mBBC.

PurposeVolumetric Modulated Arc Therapy (VMAT) exhibits potent advantages regarding target volume coverage and protection of organs at risk, notably in the context of anatomical constraints. Nevertheless, reports concerning VMAT for the treatment of synchronous bilateral breast cancers (SBBC) have been scarce to date. As such, we conducted this observational study to assess efficacy, safety and feasibility of VMAT in SBBC.Materials and MethodsFrom August 2011 to December 2017, 54 consecutive patients with SBBC with or without axillary nodes involvement underwent a treatment protocol containing radiotherapy using VMAT. A total dose (TD) of 52.2Gy in 29 fractions was delivered to breast and internal mammary chain (IMC) nodes Planning Target Volume (PTV) plus, if applicable, a TD of 49.3Gy in 29 fractions to the supra- and infra-clavicular nodes PTV and a TD of 63.22Gy in 29 fractions to tumor boost PTV. Lungs, heart, esophagus, trachea, liver, thyroid and spinal cord were considered as organs at risk. VMAT feasibility and organ at risk sparing were evaluated by treatments planning of the 20 first enrolled patients. Tolerance and patients’ outcome were prospectively monitored by acute/late toxicities records and by the analysis of overall survival (OS), locoregional recurrence-free survival (LRFS) and recurrence-free survival (RFS).ResultsBreast, supraclavicular nodes and boost PTV coverage was adequate with at least 98% of PTV encompassed by more than 95% of the prescribed dose. Less than 90% of IMC PTV was encompassed by 95% of the prescribed dose. Mean lung dose was 12.3Gy (range: 7.7 – 18.7); mean heart dose was 10.7Gy (range: 6.2 – 22.3). Concerning acute toxicities, only 2 patients experienced grade 3 skin toxicity (3.7%) and only 1 patient developed grade 1 pneumonitis. After a median follow-up of 5.3 years, grade 2 fibrosis and/or shrinking was observed in 5 patients (10%), and grade 3 fibrosis in 1 patients (2%). The 5-year LRFS-rate, RFS-rate and OS were 98% [95% CI= 86.12-99.70%], 96% [95% CI= 84.63-98.96%] and 100%, respectively.

Purpose: Lobular carcinoma in situ (LCIS) confers increased cancer risk in either breast, but it remains unclear if this population is at increased risk for bilateral breast cancer (BC) development. Here we report bilateral BC incidence among women with a history of LCIS. Methods: Women with classic-type LCIS diagnosed from 1980 to 2017 who developed unilateral BC (UBC) or bilateral BC were identified. Bilateral BC was categorized as synchronous (bilateral BC diagnosed < 6 months apart; SBBC) or metachronous (bilateral BC diagnosed ≥ 6 months apart; MBBC). Five-year incidence rates of bilateral BC among this population were evaluated. Comparisons were made to identify factors associated with bilateral BC. Results: At 7 years' median follow-up, 249/1651 (15%) women with LCIS developed BC; 34 with bilateral BC (2%). There were no clinicopathologic feature differences between those with UBC and bilateral BC. SBBC occurred in 18 without significant differences versus UBC. Among 211 with UBC and a contralateral breast at risk, 16 developed MBBC at a median follow-up of 3 years. MBBC patients were less likely to receive endocrine therapy and more likely to receive chemotherapy versus UBC. Tumor histology was not associated with MBBC. Estimated 5-year MBBC risk was 6.4%. Index estrogen/progesterone receptor positivity and endocrine therapy were the only factors associated with MBBC risk. Conclusion: Bilateral BC occurred in 2% of women with LCIS history at median follow-up of 7 years. Similar to the general BC population, a decrease in MBBC is seen among women with a history of LCIS who develop hormone receptor-positive disease and those who receive endocrine therapy, highlighting the protective effects of this treatment. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyze the association of molecular subtype concordance and disease outcome in patients with synchronous bilateral breast cancer (SBBC) and metachronous breast cancer (MBBC). Patients and methods: Patients diagnosed with SBBC or MBBC in the Surveillance, Epidemiology, and End Results (SEER) database or Comprehensive Breast Health Center (CBHC) Ruijin Hospital, Shanghai were retrospectively reviewed and included. Clinicopathologic features, molecular subtype status concordance, and prognosis were compared in patients with SBBC and MBBC. Other prognostic factors for breast cancer-specific survival (BCSS) and overall survival (OS) were also identified for bilateral breast cancer patients. Results: Totally, 3395 and 115 patients were included from the SEER and Ruijin CBHC cohorts. Molecular subtype concordance rate was higher in the SBBC group compared to MBBC in both SEER cohort (75.8% vs 57.7%, p

Abstract Background The Halcyon is a new machine from the Varian company. The purpose of this study was to evaluate the dosimetry of the Halcyon in treatment of bilateral breast cancer with volumetric modulated arc therapy. Methods On CT images of 10 patients with bilateral breast cancer, four Halcyon plans with different setup fields were generated, and dosimetric comparisons using Bonferroni’s multiple comparisons test were conducted among the four plans. Whole and partial arc plans on the Trilogy and the Halcyon, referred to as T-4arc, T-8arc, H-4arc and H-8arc, were designed. The prescription dose was 50 Gy in 2-Gy fractions. All plans were designed with the Eclipse version 15.5 treatment planning system. The dosimetric differences between whole and partial arc plans in the same accelerator were compared using the Mann–Whitney U test. The better Halcyon plan was selected for the further dosimetric comparison of the plan quality and delivery efficiency between the Trilogy and the Halcyon. Results Halcyon plans with high‐quality megavoltage cone beam CT setup fields increased the Dmean, D2 and V107 of the planning target volume (PTV) and the V5 and Dmean of the heart, left ventricle (LV) and lungs compared with other Halcyon setup plans. The mean dose and low dose volume of the heart, lungs and liver were significantly decreased in T-8arc plans compared to T-4arc plans. In terms of the V5, V20, V30, V40 and Dmean of the heart, the V20, V30, V40 and Dmean of the LV, the V30, V40, Dmax and Dmean of the left anterior descending artery (LAD), and the V5 and V40 of lungs, H-8arc was significantly higher than H-4arc (p

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Abstract Background When diagnosing patients with bilateral breast cancer, it is challenging to determine the relationship between multiple breast cancer lesions at the individual patient level with certainty. Case presentation A 35-year-old Japanese woman was diagnosed with a left breast cancer. She was previously diagnosed with right pT3N3M0 stage IIIC breast cancer and underwent chemotherapy with targeted therapy, radiotherapy, and endocrine therapy as adjuvant treatment after mastectomy and axillary lymph node dissection. Approximately 2 years after the first surgery, her left breast cancer was preoperatively diagnosed as a contralateral primary breast cancer, and left mastectomy and axillary lymph node dissection were performed. Histopathologically, the tumor was determined to be invasive ductal carcinoma accompanied with several intraductal components. After a second surgery, mutation analysis of her bilateral breast cancer was performed in a clinical study, which revealed that her metachronous bilateral breast tumors had the same GATA3 and CSMD1 mutations. Thus, mutation analysis strongly supported her latter left breast cancer being a metastatic lesion from the former right breast cancer. Some difficulties in diagnosing bilateral breast cancer exist when determining whether they are double primary cancers or represent contralateral breast metastasis. The existence of intraductal components is a critical piece of information for suspecting primary lesions. However, this case demonstrated that metastatic contralateral breast lesions can have intraductal components. Conclusion Herein we report a genetically proven contralateral breast metastasis with some intraductal components.

In the case of our patient, the synergic action of endocrine therapy and chemotherapy plus dual anti-HER2 combination allowed a complete disease control. Therapy should be scheduled by considering the two cancers as individual entities. The approach to breast cancer is changing from being considered a singular disease to a multiform one, according to current research focused on biological markers such as HER2, ERs, and PRs, with important implications in clinical, prognostic, and therapeutic features.

Objective: To evaluate the prognosis, the patient and tumor characteristics, and the treatment of bilateral breast cancer (BBC) and to compare synchronous (sBBC) and metachronous BBC (mBBC).Materials and Methods: For this retrospective study, data from 123 consecutive BBC patients (56 sBBC and 67 mBBC) that were presented at the Sion Hospital tumor board between 2007 and 2018 were collected retrospectively.Results: Mean follow-up was 85 months. 2nd tumors in both groups were more often diagnosed radiologically. Mean time interval between mBBC was 115 months. A shorter interval was positively correlated with a negative hormonal receptor (HR) status and higher grade for the 2nd tumor. There was no difference in overall survival (OS) and relapse-free survival (RFS) between sBBC and mBBC. OS was longer if both tumors were hormonal receptor (HR) positive. mBBC exhibited a higher local recurrence rate than sBBC (p=0.03).Conclusion: sBBC and mBBC patients did not show any difference in OS or RFS, although mBBC patients were more prone to local relapses.

Bilateral breast cancer (BBC), an infrequent breast cancer subtype, has primarily been studied in terms of incidence, prognosis, and through comparative analysis of synchronous (SBBC) and metachronous (MBBC) manifestations. The advent and application of organoid technology hold profound implications for tumor research and clinical management. This study represents the pioneering use of organoid models in BBC research. We established organoid lines from two surgical tumor specimens of a BBC patient, with one line undergoing detailed pathological and genomic analysis. The BBC organoid from the right breast demonstrated a marker expression profile of ER (-), PR (-), HER-2 (0), and Ki67 index 10%, indicating that it may derived from the TNBC tissue. Whole Exome Sequencing (WES) displayed consistent set of Top10 cancer driver genes affected by missense mutations, frameshift mutation, or splice site mutations in three tumor tissues and the organoid samples. The organoids' single nucleotide polymorphisms (SNPs) were more closely aligned with the TNBC tissue than other tumor tissues. Evolutionary analysis suggested that different tumor regions might evolve from a common ancestral layer. In this case, the development of BBC organoids indicated that simultaneous lesions with diverse molecular profiles shared a high degree of consistency in key tumor-driving mutations. These findings suggest the feasibility of generating BBC organoids representing various molecular types, accurately replicating significant markers and driver mutations of the originating tumor. Consequently, organoids serve as a valuable in vitro model for exploring treatment strategies and elucidating the underlying mechanisms of BBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Yao, Fang, Chen, Lian, Yao, Chen, Ji, Yu, Wang, Wang and Liang.)

Bilateral breast cancer (BBC) is an uncommon subset of breast cancer (BC), and it may present as synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). Through this study, we aimed to evaluate the proportion of BBC in BC and compare the clinicopathological characteristics, treatment, and outcomes of sBBC and mBBC at an academic cancer center in China. Patients with BC consecutively treated between 2006 and 2016 were retrospectively reviewed. Patients with BBC were included. In total, 3924 patients with BC were analyzed and 127 patients with BBC (28 sBBC, 99 mBBC) with a median follow‐up of 98 months were identified. The proportion of BBC was 3.2% (0.7%, sBBC; 2.5%, mBBC). The median age at the first diagnosis of mBBC was significantly younger than that at the first diagnosis of sBBC (p = 0.027). Patients diagnosed as having sBBC were more likely to have a positive family history (p = 0.047). The first tumors of mBBC were detected at a significantly earlier tumor stage compared with those of sBBC (p = 0.028). The concordance rates of histopathologic type in the first and second tumors were 60.7% and 58.0% in sBBC and mBBC, respectively. sBBC had a significantly poorer disease‐free survival than mBBC did (p = 0.001). BBC is a rare disease affecting the Chinese population. sBBC is associated with a greater prevalence of a family history of breast cancer and poorer prognosis, compared with mBBC. [ABSTRACT FROM AUTHOR]

Objectives. The purpose of this study was to assess and compare the clinicopathological, molecular pathology, treatment and survival characteristics in patients with metachronous bilateral breast cancer (mBBC) and synchronous breast cancer (sBBC) Materials and methods. A cohort of 658 patients with breast cancer treated at the Coltea Clinical Hospital, Surgery Department, between January 2015 and December 2019 and followed-up until August 2020 was studied. Data pertaining to patients who were diagnosed as having bilateral breast cancer were retrospectively reviewed and collected. A 3-months interval was used to distinguish metachronous from synchronous tumors. Among patients with bilateral breast cancer, assessment parameters included patient characteristics, histological and molecular pathology features and the performed treatment that were statistically evaluated comparing the first and second tumor of each group and among groups. Survival analysis was performed comparing mBBC and sBBC patients. SPSS was used for data analysis. Outcomes. Of the 658 patients with primary breast cancer, 35 (5.3%) patients were diagnosed as having bilateral breast cancer (25 (3.8%) mBBC and 10 (1.5%) sBBC). When clinical and histopathological parameters were statistically evaluated, age, menopausal status, tumor size, number of invaded nodes and anatomic stage were found to be significant between the tumors of the metachronous group and tumor size, pathologic T(tumor) and stage between tumors of the synchronous group. Hormonal receptor (HR) status concordance was higher in the synchronous group (85.7%, p = 0.010), with a higher percentage of ER positive (71.4%) and PR positive (71.4%) concordance of the tumors. In terms of survival analysis, there was a difference in overall survival (OS, p = 0.005), disease-free survival (DFS, p = 0.011) and distant relapse-free survival (p = 0.003) between mBBC and sBBC. The mean disease-free survival for patients in whom metachronous tumor occurred within less than 5 years was 63.3 months, for sBBC patients was 39.6 months, whereas for patients with more than 5 years was 437.9 months (p = 0.012, Log Rank). Discordant biomarker defined subgroup (ER,HER2) patients were associated with better disease-free survival (p = 0.047, Log Rank) and better distant relapse-free survival (p = 0.015, Log Rank) in overall patients. In terms of loco-regional relapse-free survival, although mBBC and sBBC patients showed no statistical significant difference earlier in the time course (p = 0.088, Breslow; p = 0.054 Tarone-Ware), among mBBC patients was observed a better outcome (p = 0.027, Log Rank). Conclusions. Based on survival analysis, patients in whom metachronous tumor developed after more than 5 years, had a better distant relapse-free survival. Patients with synchronous bilateral breast cancer were associated with worse disease outcome based on overall survival analysis and disease free-survival rates with more frequent rates of distant metastasis. Outcome of patients in whom metachronous tumor was diagnosed within less than 5 years might be similar to synchronous tumors. Patients with discordant ER,HER2 status showed a better disease outcome. Although concordance in HR status and molecular subtype, did not show statistical significant differences, it is a subject which deserves further clinical observation. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the association of molecular subtype concordance and disease outcome in patients with synchronous bilateral breast cancer (SBBC) and metachronous breast cancer (MBBC). Patients diagnosed with SBBC or MBBC in the Surveillance, Epidemiology, and End Results (SEER) database or Comprehensive Breast Health Center (CBHC) Ruijin Hospital, Shanghai were retrospectively reviewed and included. Clinicopathologic features, molecular subtype status concordance, and prognosis were compared in patients with SBBC and MBBC. Other prognostic factors for breast cancer-specific survival (BCSS) and overall survival (OS) were also identified for bilateral breast cancer patients. Totally, 3395 and 115 patients were included from the SEER and Ruijin CBHC cohorts. Molecular subtype concordance rate was higher in the SBBC group compared to MBBC in both SEER cohort (75.8% vs 57.7%, p < 0.001) and Ruijin CBHC cohort (76.2% vs 45.2%, p = 0.002). Survival analyses indicated that SBBC was related to worse BCSS than MBBC (p = 0.015). Molecular subtype discordance was related to worse BCSS (hazard ratio (HR), 1.64, 95% confidential interval (CI), 1.18–2.27, p = 0.003) and OS (HR, 1.59, 95% CI, 1.24–2.04, p < 0.001) in the SBBC group, but not for the MBBC group (p = 0.650 for BCSS, p = 0.669 for OS). Molecular subtype concordance rate was higher in the SBBC group than MBBC group. Patients with discordant molecular subtype was associated with worse disease outcome in the SBBC patients, but not in MBBC, which deserves further clinical evaluation. • SBBC was associated with higher concordance rates of ER, PR, HER2, and molecular subtype status compared to MBBC. • SBBC had worse BCSS than MBBC. • Molecular subtype discordance was independently related to worse prognosis in SBBC but has no impact on prognosis of MBBC. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy to bilateral breast cancer (BBC) is technically challenging because of the proximity to organs as the heart and lungs. Aim: We conducted this study tocompare helical tomotherapy (HT) to 3-dimensional conformal radiation therapy (3D-CRT) technique in bilateral chest wall irradiation regarding the coverage of target volume and the doses recorded at adjacent organs at risk. Methods: Ten patients with synchronous BBC who underwent bilateral mastectomy were included. Two plans were performed for each patient using HT and 3D-CRT. Results: Target volume included bilateral chest wall, bilateral supraclavicular and level III axillary lymph nodes. Prescription dose was 50 Gy/25 fractions in 5 weeks. The mean chest wall planning target volume (PTV) homogeneity index and conformality index were 0.15 and 1.09 in HT versus 0.37 and 1.43 in 3D-CRT plans (p= 0.012 and 0.031). At least 95% of the prescribed dose was covering 96% and 92% of the chest wall PTV for HT and 3D-CRT plans (p= 0.026). Helical tomotherapy plans achieved significant decrease in all cardiac parameters compared to 3D-CRT plans. Helical tomotherapy also achieved reduction in mean dose and V20 for both lungs in expense of higher low dose to normal healthy tissue and longer treatment time in comparison to 3D-CRT. Conclusion: For BBC patients treated with bilateral chest wall and supraclavicular lymph nodes irradiation, HT provides more conformal and homogenous plan than conventional 3D-CRT plans. Helical tomotherapy improves chest wall PTV coverage and decreases the dose to the heart and lungs in expense of more volume of normal tissues exposure to low doses of radiation and longer treatment time.

Abstract Background The incidence of bilateral breast cancer (BBC) is increasing nowadays comprising 2%‐11% of all breast cancer (BC). According to the interval time between the first and second cancer, BBC could be divided into synchronous (SBBC) and metachronous (MBBC). However, this interval time is quite different across studies. It remains controversial whether the survival of BBC, SBBC, and MBBC is similar or worse compared to that of unilateral breast cancer (UBC), and whether the survival of SBBC is similar or worse compared to MBBC. To better understand the survival of UBC, BBC, SBBC, and MBBC and how the interval time would influence the prognosis of SBBC and MBBC, we performed this meta‐analysis on studies from recent 10 years (2008‐2018). Methods Databases of PubMed, Embase, and Web of Science were searched for relevant studies within recent 10 years. Hazard ratio (HR) was adopted to evaluate the difference of overall survival (OS) of UBC, BBC, SBBC, and MBBC. HR of OS comparisons were performed between BBC vs UBC, SBBC vs UBC, MBBC vs UBC, and SBBC vs MBBC with 3, 6, 12 months as the interval time, respectively. Results There were 15 studies of 72 302 UBC and 2912 BBC included in the meta‐analysis. The summary HR of OS comparison between BBC vs UBC was 1.68 (95% CI: 1.28‐2.20), SBBC vs UBC was 2.01 (95% CI: 1.14‐3.55), MBBC vs UBC was 3.22 (95% CI: 0.75‐13.78). When 3, 6, 12 months were used as the interval time, the summary HR of the OS comparison between of SBBC vs MBBC were 0.64 (95% CI: 0.44‐0.94), 1.17 (95% CI: 0.84‐1.63) and 1.45 (95% CI: 1.10‐1.92), respectively. Conclusion BBC and SBBC showed worse prognosis in terms of OS compared to UBC while MBBC manifested similar or non‐superior survival as UBC. The OS comparison between SBBC and MBBC changed with different interval time used. The longer the interval time used, the worse the survival of SBBC. SBBC with interval of 3‐12 months between the two cancers had the worst prognosis. When 6 months was used to differentiate SBBC from MBBC, these two clinical entities showed similar OS.

Introduction. Although bilateral breast cancers are a rare condition in the general population, the incidence has increased significantly in BRCA1 and BRCA2 gene carrier breast cancer patients. Besides the genetic susceptibility, many risk factors such as age, first breast cancer diagnosis age, lifestyle, and environmental factors may be effective in the development of this type of cancer. This study aimed to determine BRCA1/2 gene carriage in patients with bilateral breast cancer and to find out the risk factors that may lead to contralateral cancer formation. Material and methods. From 2016 to 2018, in Turkey, we grouped 31 women diagnosed with bilateral breast cancer synchronously and metasynchronously. Analysis of BRCA1 and BRCA2 genes of these women evaluated for clinical and pathological tumour characteristics was performed using the NGS technique. Results. No significant difference was found between the metachronous (MBBC) and synchronous (SBBC) groups in terms of clinical and pathological tumour characteristics. MBBC patients' age at first diagnosis of breast cancer was lower than SBBC. Also, there was a statistically significant relationship between chronic diseases and MBBC cancers (c2 = 11.519; p = 0.001). In our study, disease-related variants were found only in three patients, and two of these variants were identified the first time in the literature. Conclusion. The risk of bilateral breast cancer of BRCA1/2 carriers increases when the first breast cancer is diagnosed at a young age and there is a significant family history of cancer. MBBC is associated with chronic diseases, and large-scale research will contribute to clarifying this relationship. [ABSTRACT FROM AUTHOR]

Claudins are essential components of tight junctions, which are frequently deregulated in breast cancer. The aim of the current study was to assess claudin-3 and -4 expression in bilateral breast cancer (BBC) and unilateral breast cancer (UBC). Immunohistochemical expression of claudin-3 and claudin-4 was evaluated in tissue microarrays containing 174 cases of BBCs paired with 174 cases of solitary tumors. Each case was classified as claudin-high or claudin-low depending on the H-score value. The results were correlated with histopathological features and the expression of basic breast cancer biomarkers. Median H-scores for claudin-3 were significantly higher in the synchronous BBC (sBBC) than in UBC. Claudin-4-high cases were more prevalent than within the whole BBC group, and sBBC and metachronous BBC (mBBC) alone. In the BBC group negative ER, high Ki-67 and high claudin-3 were independent factors correlated with high claudin-4. In the UBC group, Ki-67 >14% and high claudin-3 were associated with high claudin-4. Our study demonstrates that the expression of claudin-4 is significantly higher in UBC compared to BBC tumors. We also demonstrated that high claudin-4 expression in BBC is associated with a more aggressive phenotype (lack of steroid receptors, HER2 overexpression, and high Ki-67). It is possible that claudins down- and upregulation may depend on different triggers and lead to various consequences in UBC and BBC. [ABSTRACT FROM AUTHOR]

Background: The Halcyon is a new machine from the Varian company. The purpose of this study was to evaluate the dosimetry of the Halcyon in treatment of bilateral breast cancer with volumetric modulated arc therapy.Methods: On CT images of 10 patients with bilateral breast cancer, four Halcyon plans with different setup fields were generated, and dosimetric comparisons using Bonferroni's multiple comparisons test were conducted among the four plans. Whole and partial arc plans on the Trilogy and the Halcyon, referred to as T-4arc, T-8arc, H-4arc and H-8arc, were designed. The prescription dose was 50 Gy in 2-Gy fractions. All plans were designed with the Eclipse version 15.5 treatment planning system. The dosimetric differences between whole and partial arc plans in the same accelerator were compared using the Mann-Whitney U test. The better Halcyon plan was selected for the further dosimetric comparison of the plan quality and delivery efficiency between the Trilogy and the Halcyon.Results: Halcyon plans with high-quality megavoltage cone beam CT setup fields increased the Dmean, D2 and V107 of the planning target volume (PTV) and the V5 and Dmean of the heart, left ventricle (LV) and lungs compared with other Halcyon setup plans. The mean dose and low dose volume of the heart, lungs and liver were significantly decreased in T-8arc plans compared to T-4arc plans. In terms of the V5, V20, V30, V40 and Dmean of the heart, the V20, V30, V40 and Dmean of the LV, the V30, V40, Dmax and Dmean of the left anterior descending artery (LAD), and the V5 and V40 of lungs, H-8arc was significantly higher than H-4arc (p < 0.05). Compared with the Trilogy's plans, the Halcyon's plans reduced the high-dose volume of the heart and LV but increased the mean dose of the heart. For the dose of the LAD and the V20 and V30 of lungs, there was no significant difference between the two accelerators. Compared with the Trilogy, plans on the Halcyon significantly increased the skin dose but also significantly reduced the delivery time.Conclusion: For the Halcyon, the whole-arc plans have more dosimetric advantages than partial-arc plans in bilateral breast cancer radiotherapy. Although the mean dose of the heart and the skin dose are increased, the doses of the cardiac substructure and other OARs are comparable to the Trilogy, and the delivery time is significantly reduced. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular carcinoma (ILC) is less common that invasive ductal carcinoma (IDC), and more challenging to diagnose by examination and screening mammography. This study evaluated current trends in ILC incidence, and described the 5-, 10-, and 15-year survival probabilities for women diagnosed with ILC in Ontario, Canada. Methods: This retrospective cohort analysis included all women aged 18 years and older diagnosed with breast cancer between 1991 and 2015. Health administrative data from the Institute of Clinical Evaluative Sciences and the Ontario Cancer Registry were used to identify breast cancer cases. Age-adjusted incidence was plotted by year. Crude proportions were plotted by year of diagnosis for stage and hormone receptor status. Kaplan–Meier curves were generated to determine the 5-, 10-, and 15-year survival probabilities for ILC and IDC. Results: From 1991 to 2015, there were 194,065 cases of breast cancer in Ontario, 14.7% of which were ILC. The age-adjusted incidence of breast cancer increased 1.04-fold, while ILC rates increased 1.53-fold. All bilateral breast cancers were of lobular origin. The proportion of stage 1 ILC decreased, while the proportion of stage 2–4 ILC increased. The 5-, 10-, and 15-year overall survival probabilities for women diagnosed with ILC were 82.7%, 65.3%, and 50.2%, respectively. Conclusions: This study contains the largest population dataset of ILC evaluated to date. While total breast cancer incidence rates in Ontario are largely unchanged, ILC incidence rates are steadily increasing and there is a trend towards diagnosis of ILC at a later stage. These trends highlight the ongoing diagnostic and treatment challenge ILC presents for patients and clinicians. [ABSTRACT FROM AUTHOR]

Abstract Background Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours. Methods Thirty-seven invasive breast tumour pairs were stratified according to laterality and time interval between the diagnoses of the two tumours. In a multi-omics approach, tumour clonality was analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), were used to classify the tumours as clonally related recurrences or independent primary tumours. Results The SI and hierarchical clustering showed similar tendencies and the highest concordance with the other methods. Concordant evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no association was found between the current clinical guidelines and molecular tumour features. Conclusions A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. Guidelines need to be defined with exact thresholds to standardise clonality testing in a routine diagnostic setting.

Aim: The aim of the study was to find the most balanced plan with an optimal combination of planning parameters in helical tomotherapy (HT) for bilateral breast irradiation by evaluating dosimetric indices and time factors. In particular, we investigated the best combination of field width (FW), pitch, and modulation factor (MF). Materials and Methods: A total of 90 plans (18 plans for each patient) was created in this study, with different combination of planning parameters (FW: 2.5 cm [F1] and 5 cm [F2]; pitch: 0.215 [P1], 0.287 [P2], and 0.43 [P3]; and MF: 2.0 [M1], 2.5 [M2], and 3.0 [M3]). Plans were analyzed using several dosimetric indices: homogeneity index, conformity index, dose near minimum D98%, dose near maximum D2%, and the coverage by D95% of the target. Organ at risk (OAR) doses were evaluated by mean dose, V5Gy and V25Gy for the heart and mean dose V5Gy and V20Gy for both the lungs. Treatment time was also reported for all plans. Results: Reducing FW from 5 cm to 2.5 cm increased the treatment time by 40%-50% and improved homogeneity of the target. Tightening the pitch value from 0.43 to 0.215 improved target as well as OAR doses without increasing the treatment time. Increasing MF from 2 to 3 improved all the dosimetric indices and also increased treatment time. Conclusions: On the basis of our analysis, a plan with FW 5 cm, pitch 0.215, and MF 2.5 can be considered as an optimal combination of planning parameters for bilateral breast irradiation in HT technique. [ABSTRACT FROM AUTHOR]