A case report of synchronous primary bilateral breast cancer with different molecular types

A case report of synchronous primary bilateral breast cancer with different molecular types | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A case report of synchronous primary bilateral breast cancer with different molecular types Lingli Yao, Qiyuan Chen, Dongbo Shi, Jiabo Zhang, Yu Guo, Xiupeng Jia This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8999841/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The incidence of synchronous bilateral breast cancer is extremely low, and the majority of patients present with identical immunohistochemical (IHC) subtypes in both breasts. Cases with discordant IHC subtypes are relatively rare, posing significant diagnostic and therapeutic challenges. It is useful to report every case in order to establish treatment algorithms. Case presentation: In this report, we presented a74-year-old female with a history of asthma and endometrial carcinoma who diagnosed with T1N0M0 ER+, PR+, HER2- invasive ductal carcinoma in left breast and T1N3M0 TNBC invasive lobular carcinoma, for which she underwent left breast-conserving surgery with sentinel lymph node biopsy and right modified radical mastectomy with completion axillary lymph node dissection. A curative-intent treatment plan has been formulated, consisting of four cycles of doxorubicin/cyclophosphamide followed by paclitaxel (A: 80 mg/m², C: 600 mg/m² - T: 100 mg/m²) chemotherapy. Subsequently, the patient will be subjected to bilateral surgical site radiotherapy, followed by one year of low-dose capecitabine consolidation therapy and at least five years of anastrozole endocrine therapy. Conclusions: The diagnosis of synchronous primary bilateral breast cancer must be based on definitive pathological findings. Molecular subtype discordance in synchronous primary bilateral breast cancer poses unique therapeutic challenges, and no unified treatment standard currently exists. Therefore, treatment decisions require individualized consideration. Breast cancer Bilateral breast cancer Diagnosis Treatment Case report Figures Figure 1 Figure 2 Introduction Bilateral breast cancer is defined as the presence of an independent primary malignant tumor in each breast. Synchronous primary bilateral breast cancer (SBBC), typically defined as a diagnosis in both breasts within a six-month interval, comprises approximately 1%–3% of all breast cancer cases[1–4]. With significant advancements such as the widespread adoption of breast X-ray screening, MRI, improvements in breast cancer survival rates and widespread adoption of standardized contralateral breast screening, the incidence of SBBC has been increasing, having doubled over the few past decades [5]. Most studies report that 80% of SBBC patients have the same biological subtype in both breasts, with only about 20% presenting different subtypes [6]. Consequently, cases of SBBC with different histopathological and molecular structures are rare. The presence of discordance between tumors, each characterized by molecular profiles, poses a significant challenge in the selection of therapies. This report details a patient diagnosed with SBBC, whose bilateral tumors exhibited distinct pathological and molecular subtypes. The clinical characteristics, imaging findings, pathological types, molecular status, therapies and outcomes of this patient were described, which were highly individualized. Case description The patient is a 74-year-old Asian woman with a history of asthma and endometrial carcinoma, who complaining of 6-month history of a gradually enlarging, painless left breast mass. However, the physical examination revealed a 1.5 cm, no-tender, ill-defined mass in the upper inner quadrant of the right breast without skin changes and palpable mobile axillary lymph nodes (ALN). A single non-tender, firm, 1cm mass was palpable in the upper inner quadrant of the left breast without enlarged axillary lymph node. Ultrasonography(US) demonstrates a 12×8 mm, relatively regular shape, microlobulated margins, hypoechoic mass containing small patchy in the left breast at 10 o'clock position. In the right breast, a 12×4 mm hypoechoic lesion was observed near the glandular edge at the 2 o'clock position, with relatively smooth margins and suspected punctate hyperechoic foci internally (Fig. 1 ). And enlarged lymph nodes of 23 x 14mm in the right subaxillary region, with poor corticomedullary differentiation and visible dotted blood flow signals. Based on the ultrasound findings, the masses were classified as BI-RADS category 4a. Mammography showed multiple fine granular calcifications in the upper inner quadrant of the left breast, classified as BI-RADS 4b, and mild architectural distortion with granular calcifications was noted in right breast, classified as BI-RADS 4a. MRI further confirmed the presence of space-occupying lesions in the upper inner quadrants of both breasts, also categorized as BI-RADS 4a, and revealed several enlarged lymph nodes in the right axilla. Then, the patient subsequently underwent surgery under general anesthesia in November 2025. Rapid intraoperative pathological analysis confirmed bilateral breast malignancies. Initially, she underwent bilateral breast-conserving surgery with bilateral sentinel lymph node biopsy followed by right axillary lymph node dissection. Unfortunately, conventional pathology indicated positive margins on the right inner side. After multidisciplinary discussion and consideration of the positive surgical margins, the patient underwent right mastectomy. The final histopathological analysis revealed the following: Right breast: invasive lobular carcinoma (ILC) with lobular carcinoma in situ, maximum diameter 20 mm, histological grade 2, ER negative, PR negative, HER2 score 2(with no amplification in FISH), Ki-67 25%, with metastasis identified in 25 right axillary lymph nodes(SLNB 3/4, ALN22/23), pT1cN3Mx; Left breast: invasive ductal carcinoma (IDC), maximum diameter 12 mm, ER and PR strongly positive, HER2 score 2(with no amplification in FISH), Ki-67 15%, with no metastasis identified in left axillary lymph nodes(SLNB 0/3), pT1cN0Mx(Fig. 2 ). Following comprehensive evaluation, no distant metastases to the liver, lungs, bones, or brain were detected. A curative-intent treatment plan has been formulated, consisting of four cycles of doxorubicin/cyclophosphamide followed by paclitaxel (A: 80 mg/m², C: 600 mg/m² - T: 100 mg/m²) chemotherapy. Subsequently, the patient will be subjected to bilateral surgical site radiotherapy, followed by one year of low-dose capecitabine consolidation therapy and at least five years of anastrozole endocrine therapy (Table 1 ). The patient completed post-surgical systemic therapy with four cycles of the AC regimen. Due to grade 2 gastrointestinal reactions and grade 3 liver function abnormalities following chemotherapy, the doses for the subsequent two cycles were reduced. Overall, the patient was able to return to the hospital for treatment on schedule according to the established plan. Follow-up examinations, including breast ultrasound, supraclavicular lymph node ultrasound, fasting abdominal ultrasound, and tumor markers (CA125, CA153, CEA, AFP), showed no abnormalities or signs of recurrence. Table 1 Patient history review. Category Details Brief history Gender Woman Age at first visit (years) 74 Chief complaint 6-month history of a gradually enlarging, painless left breast mass Past medical history Endometrial carcinoma and Total hysterectomy Obstetric history Married with two children Family history Denied family history of breast and ovarian cancer Operation Right modified radical mastectomy with completion axillary lymph node dissection Left breast-conserving surgery with sentinel lymph node biopsy Pathological diagnosis Right breast: Invasive lobular carcinoma, T1N3M0 Left breast: Invasive ductal carcinoma, T1N0M0 Molecular subtyping Right breast: ER (−), PR (−), HER2 (++) HER2 FISH amplification (-) Ki-67 (25%) Left breast: ER (99%), PR (99%), HER2 (++), HER2 FISH amplification (-), Ki-67 (15%) Postoperative Adjuvant therapy AC-T regimen Radiotherapy (Plan) Radiotherapy for the right chest wall and right supraclavicular/infraclavicular region was delivered at a dose of 5000 cGy in 25 fractions. Radiotherapy for the left breast was administered at a dose of 5000 cGy in 25 fractions (DT 5000 cGy/25 Fx), with a simultaneous integrated boost to the tumor bed of 6000 cGy in 25 fractions. Endocrine therapy (Plan) Anastrozole intensive treatment (Plan) Capecitabine 650 mg/m², bid, po Discussion and Conclusions The diagnosis of SBBC must be based on pathological confirmation that both breast lesions are primary carcinomas. The criteria proposed by Chaudary et al. [7] as follows: (i) the presence of in situ changes in both carcinomas; (ii) different pathological types of the two carcinomas; (iii) a higher degree of differentiation in the second breast cancer compared to the first; (iv) in cases where the pathological type and degree of differentiation are identical, the absence of local, regional, or distant metastasis from the first carcinoma. Interestingly, previous retrospective studies have reported that SBBC patients more frequently exhibit ER/PR-positive and HER2-negative status [8]. Furthermore, approximately 78.9% of patients had bilateral tumors with identical molecular subtypes [9], with many presenting as Luminal-type bilateral breast cancer. If it is assumed that the bilateral tumors in SBBC are exposed to similar hormonal environments and identical external stimuli[10], leading to this phenomenon, then SBBC patients exhibiting different immunohistochemical types in bilateral tumors appear particularly noteworthy. Risk factors for SBBC include lobular histology, age at diagnosis, a family history of breast cancer in first-degree relatives and mutations in driver genes (such as BRCA1/2, CHEK2, TP53)[11–14]. The high occurrence rate of bilateral breast cancer can only be partially explained by the aforementioned driver gene mutations. From a genetic perspective, it has been confirmed that the tumors in both sides of SBBC originate independently, and its occurrence is considered as independent biological events in each breast [15, 16].But it cannot fully explain the etiology of different types of bilateral breast cancer, thus warranting further investigation. Driver genes cannot fully account for the etiology of different types of bilateral breast cancer, which requires further investigation. Multiple studies have reported poor prognosis in patients with SBBC. Compared with unilateral breast cancer (UBC) and MBBC, SBBC is associated with shorter overall survival (OS)[17, 18]. The 10-year RFS and OS rates of SBBC are significantly lower (58.1%, 70.1%) vs. UBC (91.0%, 97.2%)[19]. The disease-free survival for SBBC was 126.3 months, while for MBBC it was 243.7 months ( P = 0.041) [20]. Previous studies have that discordant hormone receptor expression between the bilateral tumors is an adverse prognostic factor in SBBC [10, 21]. In a study involving 4,403 patients with SBBC, Baretta et al. [21]reported that patients with bilateral ER-positive expression had the most favorable prognosis. The mortality rate in cases with discordant ER expression status was approximately twice that of concordant positive cases, with a 2.8-fold higher risk of death. People with bilateral negative expression had the worst prognosis. While large-scale data are lacking, Oncotype DX is a feasible gene expression profiling (GEP) tests that provide recurrence risk results; it helps determine the likely therapeutic benefit of adding chemotherapy to hormones alone in patients with early, HR positive, HER2-negative SBBC. However, due to inter-tumor heterogeneity, comprehensive evaluation is essential[22]. A study utilizing Oncotype DX for SBBC reported that 67% of patients had concordant recurrence scores (RS) who were older (median age 62 years) and had higher and more similar median PR expression levels. Notably, the discordance rate of RS reached 48.1% among women 50 years of age or younger.[23].Therefore, the Oncotype DX assay should be applied with greater caution in women under 50 years of age with bilateral breast cancer. Based on well-established guidelines for adjuvant therapy in unilateral breast cancer, a unified consensus recommends that adjuvant therapy for SBBC should be based on the side with the higher recurrence risk and more advanced stage. However, when discussing the treatment plan for this patient, several challenging issues remain. In this case report, the patient's bilateral breast tumors were entirely discordant in terms of pathology, immunohistochemical subtype, and stage. The left side was an ER and PR-positive, HER2 negative invasive ductal carcinoma, while the right side was an ER and PR-negative, HER2-negative invasive lobular carcinoma with axillary lymph node metastasis. According to the treatment plan, the patient was scheduled to receive adjuvant chemotherapy, followed by bilateral breast radiotherapy, and subsequently planned for one year of capecitabine treatment and five years of anastrozole treatment. The first question is whether adjuvant radiotherapy can be omitted for such an elderly female patient. Clinical practice guidelines recommend radiotherapy for SBBC patients with axillary lymph node metastasis or those who have undergone breast-conserving surgery. Although studies have explored the feasibility of reducing radiotherapy doses in SBBC patients to enhance lung and heart protection [24, 25]. However, due to the low occurrence rate of SBBC, there is a lack of large-sample cohort data on how to optimize organ-at-risk (OAR) doses. Based on the CALGB 9343[26] and PRIME II trials[27], the EUSOMA guidelines suggest that patients aged over 70 years with low-risk breast cancer who receive adjuvant endocrine therapy do not require radiotherapy, similar to the recommendations of the National Institute for Health and Care Excellence (NICE) and the NCCN guidelines. The results of the PRIME II trial provide additional data indicating that while omitting RT increases cumulative local recurrence, it does not significantly affect distant disease-free survival or overall survival. Correspondingly, among SBBC patients, can radiotherapy be omitted for elderly patients with early-stage HR-positive disease who are receiving endocrine therapy after breast-conserving surgery, or even for the side with a lower risk of recurrence? This represents a future direction; however, no relevant reports have been identified to date. The second question, referencing the results of the SYSUCC-001 study, involves metronomic chemotherapy for the patient's right breast and oral anastrozole for the left breast. How should the administration sequence be arranged—concurrently or sequentially? After discussion by our hospital's multidisciplinary team (MDT), considering the patient's advanced age and the locally advanced status of the right side, it was recommended that the patient prioritize a sequential administration regimen of capecitabine followed by anastrozole. In early-stage HR-positive breast cancer, delaying anastrozole initiation by 12 months may not adversely affect survival[28]. Furthermore, due to the delayed initiation of anastrozole, omitting radiotherapy on the left side is not recommended. For such complex cases of synchronous bilateral breast cancer, more systematic diagnostic and therapeutic strategies are still lacking. Conclusion Overall, SBBC exhibited the poorer overall survival with discordant molecular subtypes had an even more unfavorable prognosis especially. Currently, there is no consistent evidence-based guideline for the treatment of SBBC. These cases essentially represent bilateral interval breast cancers requiring intensive therapy. However, in bilateral breast cancer with discordant molecular subtypes, careful consideration of adjuvant treatment regimens and timing is necessary, and multidisciplinary discussion is recommended for these patients. This study reports the imaging diagnosis, pathological characteristics, and treatment course of a case of SBBC with different molecular types. Abbreviations Synchronous primary bilateral breast cancer SBBC Ultrasonography US Magnetic resonance imaging MRI Estrogen receptor ER Progesterone receptor PR Human epidermal growth factor receptor-2 HER2 Ductal carcinoma in-situ DCIS Axillary lymph nodes ALN Axillary lymph nodes dissection ALND Invasive lobular carcinoma ILC Invasive ductal carcinoma IDC Gene expression profiling GEP Organ‑at‑risk OAR Declarations Ethics approval and consent to participate The study was performed in accordance with the Declaration of Helsinki and relevant guidelines and regulations. Study participants provided informed consent and obtained ethical approval from the committee/institutional review board of The First Affiliated Hospital of Ningbo University the approved our study. (Approval Number: 2026009RS-01). Written informed consent was obtained from the patient for the publication of this case report. Consent for publication Study participants provided written informed consent for publication. Availability of data and materials The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Not applicable Authors' contributions All authors have reviewed the final version to be published and agreed to be accountable for all aspects of the work. Concept and design: Lingli Yao Acquisition, analysis, or interpretation of data: Qiyuan Chen, Dongbo Shi Drafting of the manuscript: Lingli Yao, Jiabo Zhang, Xiupeng jia Review of pathological results ： Xiupeng Jia Supervision: Yu Guo Acknowledgements Thanks to our MDT team for formulating the plan. References Jobsen, J.J., et al., Bilateral breast cancer, synchronous and metachronous; differences and outcome. Breast Cancer Res Treat, 2015. 153 (2): p. 277-83. Khalil, A.I., et al., [Synchronous bilateral breast cancer: experiences in the Mohammed VI Cancer Treatment Center, CHU Ibn Rochd, Casablanca]. Pan Afr Med J, 2016. 25 : p. 121. Kheirelseid, E.A., et al., Bilateral breast cancer: analysis of incidence, outcome, survival and disease characteristics. Breast Cancer Res Treat, 2011. 126 (1): p. 131-40. Li, X., et al., Clinical characteristics and clinicopathological correlations of bilateral breast cancer in China: A multicenter study from Chinese Society of Breast Surgery (CSBrS-006). Chin J Cancer Res, 2021. 33 (1): p. 27-32. Sakai, T., et al., National trends of synchronous bilateral breast cancer incidence in the United States. Breast Cancer Res Treat, 2019. 178 (1): p. 161-167. Schulze, A.K., et al., Tumor Characteristics of Bilateral Breast Cancer Compared with Unilateral Breast Cancer. Ann Surg Oncol, 2024. 31 (2): p. 947-956. Chaudary, M.A., et al., Bilateral primary breast cancer: a prospective study of disease incidence. Br J Surg, 1984. 71 (9): p. 711-4. Sim, Y., et al., Bilateral breast cancers in an Asian population, and a comparison between synchronous and metachronous tumours. ANZ J Surg, 2018. 88 (10): p. 982-987. Li, B., et al., A study of clinical and molecular characteristics in bilateral primary breast cancer. Cancer Med, 2023. 12 (15): p. 15881-15892. Ding, S., et al., Association of molecular subtype concordance and survival outcome in synchronous and metachronous bilateral breast cancer. Breast, 2021. 57 : p. 71-79. Narod, S.A., Bilateral breast cancers. Nat Rev Clin Oncol, 2014. 11 (3): p. 157-66. Pak, L.M., et al., Tumor phenotype and concordance in synchronous bilateral breast cancer in young women. Breast Cancer Res Treat, 2021. 186 (3): p. 815-821. Huang, X., et al., Pedigree analysis exploring the inconsistency between diverse phenotypes and testing criteria for germline TP53 mutations in Chinese women with breast cancer. Breast Cancer Res Treat, 2024. 206 (3): p. 653-666. Cybulski, C., et al., CHEK2-positive breast cancers in young Polish women. Clin Cancer Res, 2006. 12 (16): p. 4832-5. Begg, C.B., et al., Contralateral breast cancers: Independent cancers or metastases? Int J Cancer, 2018. 142 (2): p. 347-356. Hamy, A.S., et al., Evolution of synchronous female bilateral breast cancers and response to treatment. Nat Med, 2023. 29 (3): p. 646-655. Hartman, M., et al., Incidence and prognosis of synchronous and metachronous bilateral breast cancer. J Clin Oncol, 2007. 25 (27): p. 4210-6. Pan, B., et al., The prognostic comparison among unilateral, bilateral, synchronous bilateral, and metachronous bilateral breast cancer: A meta-analysis of studies from recent decade (2008-2018). Cancer Med, 2019. 8 (6): p. 2908-2918. Pan, B., et al., Long-term survival of screen-detected synchronous and metachronous bilateral non-palpable breast cancer among Chinese women: a hospital-based study (2003-2017). Breast Cancer Res Treat, 2022. 196 (2): p. 409-422. Ozturk, A., et al., Synchronous and metachronous bilateral breast cancer: A long-term experience. J buon, 2018. 23 (6): p. 1591-1600. Baretta, Z., O.I. Olopade, and D. Huo, Heterogeneity in hormone-receptor status and survival outcomes among women with synchronous and metachronous bilateral breast cancers. Breast, 2015. 24 (2): p. 131-6. Wang, J., et al., Discordance of Oncotype DX scores in synchronous bilateral and unilateral multifocal breast cancers. Breast Cancer Res Treat, 2024. 203 (1): p. 73-83. Karsten, M., et al., Oncotype DX in Bilateral Synchronous Primary Invasive Breast Cancer. Ann Surg Oncol, 2016. 23 (2): p. 471-6. Yamauchi, C., et al., Bilateral breast-conserving therapy for bilateral breast cancer: results and consideration of radiation technique. Breast Cancer, 2005. 12 (2): p. 135-9. Wadasadawala, T., et al., Use of tomotherapy in treatment of synchronous bilateral breast cancer: dosimetric comparison study. Br J Radiol, 2015. 88 (1048): p. 20140612. Hughes, K.S., et al., Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol, 2013. 31 (19): p. 2382-7. Kunkler, I.H., et al., Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer. N Engl J Med, 2023. 388 (7): p. 585-594. Lee, K.T., et al., Effect of delays in initiation of adjuvant endocrine therapy on survival among women with breast cancer. Breast Cancer Res Treat, 2020. 184 (3): p. 965-975. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8999841","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":614534556,"identity":"1d983658-0a0a-40b8-98c2-b286203aa318","order_by":0,"name":"Lingli Yao","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Lingli","middleName":"","lastName":"Yao","suffix":""},{"id":614534557,"identity":"6660d6f0-3045-4a9d-9e5b-268dc91a79a7","order_by":1,"name":"Qiyuan Chen","email":"","orcid":"","institution":"Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Qiyuan","middleName":"","lastName":"Chen","suffix":""},{"id":614534558,"identity":"4ef9ad7f-180b-4c3b-b9b6-c725cca61122","order_by":2,"name":"Dongbo Shi","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Dongbo","middleName":"","lastName":"Shi","suffix":""},{"id":614534559,"identity":"e945de9b-983d-46a7-8698-e83f499dcc01","order_by":3,"name":"Jiabo Zhang","email":"","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":false,"prefix":"","firstName":"Jiabo","middleName":"","lastName":"Zhang","suffix":""},{"id":614534560,"identity":"a883a8aa-8ef5-4677-8c18-b5486f77db08","order_by":4,"name":"Yu Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYNCCHxJy/MzMhx8Qr4Oxx8ZYsp0tzYAEW9jSEjec51GQIEqxfETyMWkensPGxod5GAwYamyiCWoxvJGWJs1jcVjO7DDvgQcMx9JyGwhqmZFjBrbF7DBfggFjw2FitbAdTtzczGMgQZQWeQmwFqD3mYnVYsDzLNlyLjCQJQ4DAzmBGL/ItycfvPEGFJX9hw8/+FBjQ4QtBxhYENGRQEg52JYGBuYPxCgcBaNgFIyCEQwASiY7AmZzNuAAAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Ningbo University","correspondingAuthor":true,"prefix":"","firstName":"Yu","middleName":"","lastName":"Guo","suffix":""},{"id":614534561,"identity":"c19ba447-7315-43d9-92c0-ebac02fbcf8f","order_by":5,"name":"Xiupeng Jia","email":"","orcid":"","institution":"Ningbo Clinical Pathology Diagnosis Center","correspondingAuthor":false,"prefix":"","firstName":"Xiupeng","middleName":"","lastName":"Jia","suffix":""}],"badges":[],"createdAt":"2026-03-01 07:38:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8999841/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8999841/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105982859,"identity":"f4462599-ff9d-4b2b-85a4-004eb134943d","added_by":"auto","created_at":"2026-04-02 07:05:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":840126,"visible":true,"origin":"","legend":"\u003cp\u003eThe imaging features of the breast (A)In the US graph of right breast, a 12×4 mm hypoechoic lesion was observed near the glandular edge at the 2 o'clock position, with relatively smooth margins and suspected punctate hyperechoic foci internally. (B)US demonstrates a 12×8mm, relatively regular shape, microlobulated margins, hypoechoic mass containing small patchy in the left breast .(C)Enlarged \u0026nbsp;lymph nodes in right axillary (D)Breast contrast-enhanced magnetic resonance imaging (MRI) revealed a hyperintense lesion in the left breast measuring approximately 12×12 mm, with clear and smooth margins, and a hyperintense lesion measuring approximately 11×9 mm was identified, with indistinct margins in right breast.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8999841/v1/baa951c3c233847f1726b3d8.png"},{"id":106094346,"identity":"de19714b-792e-45c6-8404-8ffef882bbc2","added_by":"auto","created_at":"2026-04-03 11:42:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1339723,"visible":true,"origin":"","legend":"\u003cp\u003eThe histopathological immunohistochemical images of the breast tumor tissue. (A) HE staining shows ILC in right breast. (B) HE staining shows invasive ductal carcinoma in left breast. (C, D) Original magnification × 400: Tumor cells in right breast showing negative for ER/PR by IHC analysis. (E, H, I, J) Original magnification × 400: Tumor cells in right breast showing HER2 score 2, with no amplification in FISH. (F, G) Original magnification × 400: Tumor cells in left breast showing positivity for ER/PR by IHC analysis.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8999841/v1/a0cb8fc41d7e408ca2e8d037.png"},{"id":108490919,"identity":"161c1ea7-4b79-4eb1-9386-8712dfadcea0","added_by":"auto","created_at":"2026-05-05 09:49:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2717127,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8999841/v1/bc07532f-ec46-4181-9fe8-a173a79915d7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case report of synchronous primary bilateral breast cancer with different molecular types","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBilateral breast cancer is defined as the presence of an independent primary malignant tumor in each breast. Synchronous primary bilateral breast cancer (SBBC), typically defined as a diagnosis in both breasts within a six-month interval, comprises approximately 1%\u0026ndash;3% of all breast cancer cases[1\u0026ndash;4]. With significant advancements such as the widespread adoption of breast X-ray screening, MRI, improvements in breast cancer survival rates and widespread adoption of standardized contralateral breast screening, the incidence of SBBC has been increasing, having doubled over the few past decades [5]. Most studies report that 80% of SBBC patients have the same biological subtype in both breasts, with only about 20% presenting different subtypes [6]. Consequently, cases of SBBC with different histopathological and molecular structures are rare. The presence of discordance between tumors, each characterized by molecular profiles, poses a significant challenge in the selection of therapies. This report details a patient diagnosed with SBBC, whose bilateral tumors exhibited distinct pathological and molecular subtypes. The clinical characteristics, imaging findings, pathological types, molecular status, therapies and outcomes of this patient were described, which were highly individualized.\u003c/p\u003e"},{"header":"Case description","content":"\u003cp\u003eThe patient is a 74-year-old Asian woman with a history of asthma and endometrial carcinoma, who complaining of 6-month history of a gradually enlarging, painless left breast mass. However, the physical examination revealed a 1.5 cm, no-tender, ill-defined mass in the upper inner quadrant of the right breast without skin changes and palpable mobile axillary lymph nodes (ALN). A single non-tender, firm, 1cm mass was palpable in the upper inner quadrant of the left breast without enlarged axillary lymph node. Ultrasonography(US) demonstrates a 12×8 mm, relatively regular shape, microlobulated margins, hypoechoic mass containing small patchy in the left breast at 10 o'clock position. In the right breast, a 12×4 mm hypoechoic lesion was observed near the glandular edge at the 2 o'clock position, with relatively smooth margins and suspected punctate hyperechoic foci internally (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). And enlarged lymph nodes of 23 x 14mm in the right subaxillary region, with poor corticomedullary differentiation and visible dotted blood flow signals. Based on the ultrasound findings, the masses were classified as BI-RADS category 4a. Mammography showed multiple fine granular calcifications in the upper inner quadrant of the left breast, classified as BI-RADS 4b, and mild architectural distortion with granular calcifications was noted in right breast, classified as BI-RADS 4a. MRI further confirmed the presence of space-occupying lesions in the upper inner quadrants of both breasts, also categorized as BI-RADS 4a, and revealed several enlarged lymph nodes in the right axilla.\u003c/p\u003e \u003cp\u003eThen, the patient subsequently underwent surgery under general anesthesia in November 2025. Rapid intraoperative pathological analysis confirmed bilateral breast malignancies. Initially, she underwent bilateral breast-conserving surgery with bilateral sentinel lymph node biopsy followed by right axillary lymph node dissection. Unfortunately, conventional pathology indicated positive margins on the right inner side. After multidisciplinary discussion and consideration of the positive surgical margins, the patient underwent right mastectomy.\u003c/p\u003e \u003cp\u003eThe final histopathological analysis revealed the following: Right breast: invasive lobular carcinoma (ILC) with lobular carcinoma in situ, maximum diameter 20 mm, histological grade 2, ER negative, PR negative, HER2 score 2(with no amplification in FISH), Ki-67 25%, with metastasis identified in 25 right axillary lymph nodes(SLNB 3/4, ALN22/23), pT1cN3Mx; Left breast: invasive ductal carcinoma (IDC), maximum diameter 12 mm, ER and PR strongly positive, HER2 score 2(with no amplification in FISH), Ki-67 15%, with no metastasis identified in left axillary lymph nodes(SLNB 0/3), pT1cN0Mx(Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Following comprehensive evaluation, no distant metastases to the liver, lungs, bones, or brain were detected. A curative-intent treatment plan has been formulated, consisting of four cycles of doxorubicin/cyclophosphamide followed by paclitaxel (A: 80 mg/m², C: 600 mg/m² - T: 100 mg/m²) chemotherapy. Subsequently, the patient will be subjected to bilateral surgical site radiotherapy, followed by one year of low-dose capecitabine consolidation therapy and at least five years of anastrozole endocrine therapy (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient completed post-surgical systemic therapy with four cycles of the AC regimen. Due to grade 2 gastrointestinal reactions and grade 3 liver function abnormalities following chemotherapy, the doses for the subsequent two cycles were reduced. Overall, the patient was able to return to the hospital for treatment on schedule according to the established plan. Follow-up examinations, including breast ultrasound, supraclavicular lymph node ultrasound, fasting abdominal ultrasound, and tumor markers (CA125, CA153, CEA, AFP), showed no abnormalities or signs of recurrence.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003c/div\u003e\u003ctable id=\"Tab1\" border=\"1\"\u003e \u003ccaption\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient history review.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003c/colgroup\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\"\u003e \u003cp\u003eDetails\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eBrief history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eWoman\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAge at first visit (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eChief complaint\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e6-month history of a gradually enlarging, painless left breast mass\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePast medical history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eEndometrial carcinoma and Total hysterectomy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eObstetric history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eMarried with two children\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eFamily history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eDenied family history of breast and ovarian cancer\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eOperation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRight modified radical mastectomy with completion axillary lymph node dissection\u003c/p\u003e \u003cp\u003eLeft breast-conserving surgery with sentinel lymph node biopsy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003ePathological diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRight breast: Invasive lobular carcinoma, T1N3M0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eLeft breast: Invasive ductal carcinoma, T1N0M0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eMolecular subtyping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRight breast:\u0026nbsp;ER (−), PR (−), HER2 (++)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eHER2 FISH amplification (-) Ki-67 (25%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eLeft breast: ER (99%), PR (99%), HER2 (++),\u003c/p\u003e \u003cp\u003eHER2 FISH amplification (-), Ki-67 (15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003e\u003cb\u003ePostoperative\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAdjuvant therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAC-T regimen\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRadiotherapy (Plan)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRadiotherapy for the right chest wall and right supraclavicular/infraclavicular region was delivered at a dose of 5000 cGy in 25 fractions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eRadiotherapy for the left breast was administered at a dose of 5000 cGy in 25 fractions (DT 5000 cGy/25 Fx), with a simultaneous integrated boost to the tumor bed of 6000 cGy in 25 fractions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eEndocrine therapy (Plan)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eAnastrozole\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eintensive treatment (Plan)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\"\u003e \u003cp\u003eCapecitabine 650 mg/m², bid, po\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e "},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThe diagnosis of SBBC must be based on pathological confirmation that both breast lesions are primary carcinomas. The criteria proposed by Chaudary et al. [7] as follows: (i) the presence of in situ changes in both carcinomas; (ii) different pathological types of the two carcinomas; (iii) a higher degree of differentiation in the second breast cancer compared to the first; (iv) in cases where the pathological type and degree of differentiation are identical, the absence of local, regional, or distant metastasis from the first carcinoma. Interestingly, previous retrospective studies have reported that SBBC patients more frequently exhibit ER/PR-positive and HER2-negative status [8]. Furthermore, approximately 78.9% of patients had bilateral tumors with identical molecular subtypes [9], with many presenting as Luminal-type bilateral breast cancer. If it is assumed that the bilateral tumors in SBBC are exposed to similar hormonal environments and identical external stimuli[10], leading to this phenomenon, then SBBC patients exhibiting different immunohistochemical types in bilateral tumors appear particularly noteworthy. Risk factors for SBBC include lobular histology, age at diagnosis, a family history of breast cancer in first-degree relatives and mutations in driver genes (such as BRCA1/2, CHEK2, TP53)[11–14]. The high occurrence rate of bilateral breast cancer can only be partially explained by the aforementioned driver gene mutations. From a genetic perspective, it has been confirmed that the tumors in both sides of SBBC originate independently, and its occurrence is considered as independent biological events in each breast [15, 16].But it cannot fully explain the etiology of different types of bilateral breast cancer, thus warranting further investigation. Driver genes cannot fully account for the etiology of different types of bilateral breast cancer, which requires further investigation.\u003c/p\u003e\u003cp\u003eMultiple studies have reported poor prognosis in patients with SBBC. Compared with unilateral breast cancer (UBC) and MBBC, SBBC is associated with shorter overall survival (OS)[17, 18]. The 10-year RFS and OS rates of SBBC are significantly lower (58.1%, 70.1%) vs. UBC (91.0%, 97.2%)[19]. The disease-free survival for SBBC was 126.3 months, while for MBBC it was 243.7 months (\u003cem\u003eP\u003c/em\u003e = 0.041) [20]. Previous studies have that discordant hormone receptor expression between the bilateral tumors is an adverse prognostic factor in SBBC [10, 21]. In a study involving 4,403 patients with SBBC, Baretta et al. [21]reported that patients with bilateral ER-positive expression had the most favorable prognosis. The mortality rate in cases with discordant ER expression status was approximately twice that of concordant positive cases, with a 2.8-fold higher risk of death. People with bilateral negative expression had the worst prognosis. While large-scale data are lacking, Oncotype DX is a feasible gene expression profiling (GEP) tests that provide recurrence risk results; it helps determine the likely therapeutic benefit of adding chemotherapy to hormones alone in patients with early, HR positive, HER2-negative SBBC. However, due to inter-tumor heterogeneity, comprehensive evaluation is essential[22]. A study utilizing Oncotype DX for SBBC reported that 67% of patients had concordant recurrence scores (RS) who were older (median age 62 years) and had higher and more similar median PR expression levels. Notably, the discordance rate of RS reached 48.1% among women 50 years of age or younger.[23].Therefore, the Oncotype DX assay should be applied with greater caution in women under 50 years of age with bilateral breast cancer.\u003c/p\u003e\u003cp\u003eBased on well-established guidelines for adjuvant therapy in unilateral breast cancer, a unified consensus recommends that adjuvant therapy for SBBC should be based on the side with the higher recurrence risk and more advanced stage. However, when discussing the treatment plan for this patient, several challenging issues remain. In this case report, the patient's bilateral breast tumors were entirely discordant in terms of pathology, immunohistochemical subtype, and stage. The left side was an ER and PR-positive, HER2 negative invasive ductal carcinoma, while the right side was an ER and PR-negative, HER2-negative invasive lobular carcinoma with axillary lymph node metastasis. According to the treatment plan, the patient was scheduled to receive adjuvant chemotherapy, followed by bilateral breast radiotherapy, and subsequently planned for one year of capecitabine treatment and five years of anastrozole treatment. The first question is whether adjuvant radiotherapy can be omitted for such an elderly female patient. Clinical practice guidelines recommend radiotherapy for SBBC patients with axillary lymph node metastasis or those who have undergone breast-conserving surgery. Although studies have explored the feasibility of reducing radiotherapy doses in SBBC patients to enhance lung and heart protection [24, 25]. However, due to the low occurrence rate of SBBC, there is a lack of large-sample cohort data on how to optimize organ-at-risk (OAR) doses. Based on the CALGB 9343[26] and PRIME II trials[27], the EUSOMA guidelines suggest that patients aged over 70 years with low-risk breast cancer who receive adjuvant endocrine therapy do not require radiotherapy, similar to the recommendations of the National Institute for Health and Care Excellence (NICE) and the NCCN guidelines. The results of the PRIME II trial provide additional data indicating that while omitting RT increases cumulative local recurrence, it does not significantly affect distant disease-free survival or overall survival. Correspondingly, among SBBC patients, can radiotherapy be omitted for elderly patients with early-stage HR-positive disease who are receiving endocrine therapy after breast-conserving surgery, or even for the side with a lower risk of recurrence? This represents a future direction; however, no relevant reports have been identified to date. The second question, referencing the results of the SYSUCC-001 study, involves metronomic chemotherapy for the patient's right breast and oral anastrozole for the left breast. How should the administration sequence be arranged—concurrently or sequentially? After discussion by our hospital's multidisciplinary team (MDT), considering the patient's advanced age and the locally advanced status of the right side, it was recommended that the patient prioritize a sequential administration regimen of capecitabine followed by anastrozole. In early-stage HR-positive breast cancer, delaying anastrozole initiation by 12 months may not adversely affect survival[28]. Furthermore, due to the delayed initiation of anastrozole, omitting radiotherapy on the left side is not recommended. For such complex cases of synchronous bilateral breast cancer, more systematic diagnostic and therapeutic strategies are still lacking.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOverall, SBBC exhibited the poorer overall survival with discordant molecular subtypes had an even more unfavorable prognosis especially. Currently, there is no consistent evidence-based guideline for the treatment of SBBC. These cases essentially represent bilateral interval breast cancers requiring intensive therapy. However, in bilateral breast cancer with discordant molecular subtypes, careful consideration of adjuvant treatment regimens and timing is necessary, and multidisciplinary discussion is recommended for these patients. This study reports the imaging diagnosis, pathological characteristics, and treatment course of a case of SBBC with different molecular types.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eSynchronous primary bilateral breast cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;SBBC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eUltrasonography\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eUS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eMagnetic resonance imaging\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eMRI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eEstrogen receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eProgesterone receptor\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eHuman epidermal growth factor receptor-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eHER2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eDuctal carcinoma in-situ\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eDCIS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eAxillary lymph nodes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eALN\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eAxillary lymph nodes dissection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eALND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eInvasive lobular carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eILC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eGene expression profiling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eGEP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 277px;\"\u003e\n \u003cp\u003eOrgan‑at‑risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003eOAR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was performed in accordance with the Declaration of Helsinki and relevant guidelines and regulations. Study participants provided informed consent and obtained ethical approval from the committee/institutional review board of The First Affiliated Hospital of Ningbo University the approved our study. (Approval Number: 2026009RS-01). Written informed consent was obtained from the patient for the publication of this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy participants provided written informed consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcept and design:\u0026nbsp;\u003c/strong\u003eLingli Yao\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcquisition, analysis, or interpretation of data:\u003c/strong\u003e Qiyuan Chen, Dongbo Shi\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrafting of the manuscript:\u0026nbsp;\u003c/strong\u003eLingli Yao, Jiabo Zhang, Xiupeng jia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReview of pathological results\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003eXiupeng Jia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupervision:\u0026nbsp;\u003c/strong\u003eYu Guo\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThanks to our MDT team for formulating the plan.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJobsen, J.J., et al., \u003cem\u003eBilateral breast cancer, synchronous and metachronous; differences and outcome.\u003c/em\u003e Breast Cancer Res Treat, 2015. \u003cstrong\u003e153\u003c/strong\u003e(2): p. 277-83.\u003c/li\u003e\n\u003cli\u003eKhalil, A.I., et al., \u003cem\u003e[Synchronous bilateral breast cancer: experiences in the Mohammed VI Cancer Treatment Center, CHU Ibn Rochd, Casablanca].\u003c/em\u003e Pan Afr Med J, 2016. \u003cstrong\u003e25\u003c/strong\u003e: p. 121.\u003c/li\u003e\n\u003cli\u003eKheirelseid, E.A., et al., \u003cem\u003eBilateral breast cancer: analysis of incidence, outcome, survival and disease characteristics.\u003c/em\u003e Breast Cancer Res Treat, 2011. 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Olopade, and D. Huo, \u003cem\u003eHeterogeneity in hormone-receptor status and survival outcomes among women with synchronous and metachronous bilateral breast cancers.\u003c/em\u003e Breast, 2015. \u003cstrong\u003e24\u003c/strong\u003e(2): p. 131-6.\u003c/li\u003e\n\u003cli\u003eWang, J., et al., \u003cem\u003eDiscordance of Oncotype DX scores in synchronous bilateral and unilateral multifocal breast cancers.\u003c/em\u003e Breast Cancer Res Treat, 2024. \u003cstrong\u003e203\u003c/strong\u003e(1): p. 73-83.\u003c/li\u003e\n\u003cli\u003eKarsten, M., et al., \u003cem\u003eOncotype DX in Bilateral Synchronous Primary Invasive Breast Cancer.\u003c/em\u003e Ann Surg Oncol, 2016. \u003cstrong\u003e23\u003c/strong\u003e(2): p. 471-6.\u003c/li\u003e\n\u003cli\u003eYamauchi, C., et al., \u003cem\u003eBilateral breast-conserving therapy for bilateral breast cancer: results and consideration of radiation technique.\u003c/em\u003e Breast Cancer, 2005. \u003cstrong\u003e12\u003c/strong\u003e(2): p. 135-9.\u003c/li\u003e\n\u003cli\u003eWadasadawala, T., et al., \u003cem\u003eUse of tomotherapy in treatment of synchronous bilateral breast cancer: dosimetric comparison study.\u003c/em\u003e Br J Radiol, 2015. \u003cstrong\u003e88\u003c/strong\u003e(1048): p. 20140612.\u003c/li\u003e\n\u003cli\u003eHughes, K.S., et al., \u003cem\u003eLumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.\u003c/em\u003e J Clin Oncol, 2013. \u003cstrong\u003e31\u003c/strong\u003e(19): p. 2382-7.\u003c/li\u003e\n\u003cli\u003eKunkler, I.H., et al., \u003cem\u003eBreast-Conserving Surgery with or without Irradiation in Early Breast Cancer.\u003c/em\u003e N Engl J Med, 2023. \u003cstrong\u003e388\u003c/strong\u003e(7): p. 585-594.\u003c/li\u003e\n\u003cli\u003eLee, K.T., et al., \u003cem\u003eEffect of delays in initiation of adjuvant endocrine therapy on survival among women with breast cancer.\u003c/em\u003e Breast Cancer Res Treat, 2020. \u003cstrong\u003e184\u003c/strong\u003e(3): p. 965-975. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, Bilateral breast cancer, Diagnosis, Treatment, Case report","lastPublishedDoi":"10.21203/rs.3.rs-8999841/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8999841/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThe incidence of synchronous bilateral breast cancer is extremely low, and the majority of patients present with identical immunohistochemical (IHC) subtypes in both breasts. Cases with discordant IHC subtypes are relatively rare, posing significant diagnostic and therapeutic challenges. It is useful to report every case in order to establish treatment algorithms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e In this report, we presented a74-year-old female with a history of asthma and endometrial carcinoma who diagnosed with T1N0M0 ER+, PR+, HER2- invasive ductal carcinoma in left breast and T1N3M0 TNBC invasive lobular carcinoma, for which she underwent left breast-conserving surgery with sentinel lymph node biopsy and right modified radical mastectomy with completion axillary lymph node dissection. A curative-intent treatment plan has been formulated, consisting of four cycles of doxorubicin/cyclophosphamide followed by paclitaxel (A: 80 mg/m², C: 600 mg/m² - T: 100 mg/m²) chemotherapy. Subsequently, the patient will be subjected to bilateral surgical site radiotherapy, followed by one year of low-dose capecitabine consolidation therapy and at least five years of anastrozole endocrine therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThe diagnosis of synchronous primary bilateral breast cancer must be based on definitive pathological findings. Molecular subtype discordance in synchronous primary bilateral breast cancer poses unique therapeutic challenges, and no unified treatment standard currently exists. Therefore, treatment decisions require individualized consideration.\u003c/p\u003e","manuscriptTitle":"A case report of synchronous primary bilateral breast cancer with different molecular types","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 07:05:55","doi":"10.21203/rs.3.rs-8999841/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ea1ab45e-6c63-4653-bb58-b3ee71513801","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T23:53:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 07:05:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8999841","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8999841","identity":"rs-8999841","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}