Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers

Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers | 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 Research Article Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers Akemi Morimoto, Takashi Matsumoto, Norifumi Teramoto, Sakiko Murakami, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7947639/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Apr, 2026 Read the published version in Journal of Ovarian Research → Version 1 posted 9 You are reading this latest preprint version Abstract Objective Homologous recombination (HR) status plays a pivotal role in the management of advanced ovarian, fallopian tube, and primary peritoneal cancers (collectively referred to as ovarian cancers), influencing treatment selection and response to PARP inhibitors. For patients undergoing neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS), clinicians have two opportunities to obtain tumor samples: before and after NAC. This study aimed to compare pre- and post-NAC samples to assess the impact of chemotherapy on HR status. Methods Between 2020 and 2023, 128 patients with ovarian cancer were treated at our institution. Among them, 24 underwent NAC followed by IDS. Tumor samples were analyzed using the Myriad myChoice® assay to determine genomic instability scores (GIS) and BRCA mutation status. Results Post-NAC HR status was unavailable in 8 of 24 patients (33%) due to insufficient or degraded samples. Among the 15 patients with paired pre- and post-NAC samples, BRCA mutation status remained unchanged. However, GIS scores were significantly reduced in HR-deficient (HRD) tumors after NAC, whereas HR-proficient (HRP) tumors showed no significant change. Notably, two patients converted from HRD to HRP status, with GIS decreasing from 51 to 34 in one and from 49 to 41 in the other, crossing the HRD threshold of 42. Conclusions NAC can reduce GIS and alter HR status in HRD tumors. Although post-NAC assessment may help refine treatment strategies after IDS, tissue availability is often limited. Moreover, conversion from HRD to HRP status following NAC may restrict eligibility for HR-targeted therapies. homologous recombination deficiency (HRD) ovarian cancer neoadjuvant chemotherapy interval debulking surgery genomic instability score (GIS) Figures Figure 1 Figure 2 Background Ovarian, fallopian tube, and primary peritoneal cancers (collectively referred to as ovarian cancers) are the most lethal gynecological cancers in women and are the eighth leading cause of cancer-related death [ 1 ]. The overall survival rates of advanced ovarian cancers are 42% for stage III and 26% for stage Ⅳ [ 2 ]. Currently, the standard chemotherapy for newly diagnosed advanced ovarian cancer patients is platinum-based chemotherapy, either in combination with bevacizumab [ 3 ]. While cytoreductive surgery followed by chemotherapy is the standard treatment, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) is considered for stage III and IV patients with poor surgical candidates, advanced disease, poor general condition, and surgical difficulty. Given the high recurrence rates, ovarian cancer patients often require additional treatment options following initial chemotherapy. Since 2014, PARP inhibitors have become standard maintenance therapy, significantly improving progression-free survival (PFS) and/or overall survival (OS) in ovarian cancer patients. Initially developed as DNA repair inhibitors, PARP inhibitors were designed to induce synthetic lethality in tumors with BRCA mutations or homologous recombination (HR) deficiencies. However, their clinical indications now extend beyond BRCA mutations and HR deficiencies (HRD), as BRCA wild-type and HR-proficient (HRP) cancers may also benefit from PARP inhibitors [ 4 ]. The indications for PARP inhibitors are complex and vary depending on the specific drug (e.g., olaparib, niraparib, rucaparib, talazoparib) and the tumor's HR status. For instance, based on the PAOLA-1 trial [ 5 ], the combination of bevacizumab and olaparib has been approved for HRD-associated advanced ovarian cancers in the first-line setting. Similarly, the SOLO1 trial led to the approval of olaparib for first-line treatment in patients with germline BRCA1/2 (gBRCA1/2) mutations [ 6 ]. Olaparib has also been approved for recurrent ovarian cancers regardless of HR status, based on the SOLO-2 and Study 19 trials, while niraparib received first-line approval irrespective of HR status through the PRIMA trial [ 7 ]. Thus, HR status serves as a critical determinant in selecting post-chemotherapy maintenance treatment options for advanced ovarian cancers. Although various methods are available globally to determine HR status, the Myriad myChoice assay (Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA) [ 8 ] is the only companion diagnostic system approved in Japan. The myChoice assay defines HRD as either a genomic instability score (GIS) of ≥ 42 or the presence of a tumor BRCA (tBRCA) mutation, while a GIS of < 42 is classified as HRP [ 9 ]. GIS is considered stable and reflective of genomic instability scars, and a study reports that HR status was maintained between primary and recurrent lesions in 50 pairs of high-grade serous ovarian carcinoma (HGSOC) samples [ 10 ]. For patients undergoing NAC followed by IDS, clinicians have two opportunities to obtain tumor samples: before and after NAC. In this study, we analyzed ovarian cancer patients who underwent NAC followed by IDS, focusing on both their tissues submitted for HR analysis. Our findings indicate that NAC can reduce GIS scores and alter HR status preferentially in HRD cases, and we highlight the frequent unavailability of tissue samples after NAC. Methods 2.1. Patients and study design This retrospective study was approved by the Institutional Review Board of Ehime University Hospital (approval number: 2212007). Written informed consent was obtained from participants whenever possible. For cases where obtaining individual consent was not feasible, an opt-out approach was applied in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan. The study was conducted in accordance with the principles of the Declaration of Helsinki. We enrolled a total of 128 patients with advanced ovarian, fallopian tube, and primary peritoneal cancers treated at Ehime University Hospital from November 2020 to April 2023. We obtained written informed consent from all patients before the enrollment. International Federation of Gynecology and Obstetrics (FIGO) 2014 [ 11 ] was applied to stage the cancers. We then selected 24 patients who underwent NAC followed by IDS for further analysis. 2.2. Sample analysis Cancer tissues obtained at surgery or biopsy were submitted to Myriad myChoice® assay, and we obtained GIS and tBRCA mutation status. According to the guidance of HRD companion diagnostic test available from Myriad genetics, we defined HRD as either a GIS of ≥ 42 or the presence of tBRCA mutation, while a GIS of < 42 was classified as HRP. A comparison of GIS change before and after NAC in each patient was carried out using the Welch paired t-test. A comparison of overall GIS change before and after NAC was carried out using the unpaired Student t-test. P values < 0.05 were considered to indicate statistical significance. Results Clinical and pathological characteristics of the study population In our cohort, 61 out of 128 ovarian cancer patients (47.6%) were classified as FIGO stage III or IV (Fig. 1 ). Among these, 24 patients (39.3%) underwent platinum-based NAC followed by IDS and were included in further analyses (Fig. 1 , Table 1 ). The median age of the patients was 67 years (range: 49–78). Diagnoses included ovarian cancer in 18 patients, fallopian tube cancer in 2 patients, and primary peritoneal cancer in 4 patients. FIGO stages were distributed as follows: IIIB (1 patient), IIIC (10 patients), IVA (4 patients), and IVB (9 patients). The histological type was high-grade serous ovarian carcinoma (HGSOC) in all but one patient, who had large cell neuroendocrine carcinoma (LCNEC). All patients received platinum-based chemotherapy, consisting of standard doses of carboplatin (AUC6) and paclitaxel (175 mg/m²) on day 1 of a 21-day cycle. The median number of NAC cycles completed was 5 (range: 3–7). Table 1. Clinical and pathological characteristics. (n = 24) Median age (range) 67 (49–78) Site Ovary 18 Fallopian tube 2 Peritoneal 4 Stage ⅢB 1 ⅢC 10 ⅣA 4 ⅣB 9 Histology high-grade serous carcinoma 23 LCNEC 1 Median NAC cycle (range) 5 (3–7) NAC regimen TC 24 NAC: neoadjyuvant chemotherapy, TC: paclitaxel + carboplatin, LCNEC: large cell neuroendocrine carcinoma Poor availability of tissue samples after NAC To investigate the dynamics of HR status based on GIS and tBRCA mutation status, we attempted to obtain this information both pre- and post-NAC (Table 2). However, HR status was not determinable in 2/24 (8.3%) pre-NAC cases (patients #23 and #24) due to insufficient tumor tissue in the biopsy samples. There is one case (patient #8) who failed to obtain a GIS score, yet the case had tBRCA2 mutation status, which was insufficient to determine the HR status. At a post-NAC stage, HR status was unavailable or undeterminable in 8/24 (33%) cases (patients #4, #6–8, #10, #13, #20, and #24). In detail, tBRCA mutation status was unavailable in 7/24 (28%) cases, and GIS scores were unavailable or undeterminable in 8/24 (33%) cases. The reasons are the following: pathological complete response (CR) in 2 cases (patients #6 and #24), insufficient tumor volume in IDS samples in 4 cases due to good response (patients #4, #7, #8 and #13), difficulty removing the tumor during IDS in 1 case (patient #10), and insufficient tumor tissue in 1 case (patient #20). As a result, paired HR status, pre- and post-NAC, were successfully obtained in only 15/24 (62.5%) cases. These findings highlight the challenges that clinicians face in acquiring tumor samples, particularly following NAC. Table 2 Dynamics of HR status pre- and post-chemotherapy patient # HR status BRCA signature Genomic Instability Score Clinical chemotherapy response Histology pre post pre post pre post 1 HRD HRD tBRCA1 tBRCA1 73 62 PR HGSC 2 HRD HRD tBRCA1 tBRCA1 67 63 PR HGSC 3 HRD HRD tBRCA1 tBRCA1 63 49 PR HGSC 4 HRD NA tBRCA1 NA 63 NA CR HGSC 5 HRD HRD tBRCA1 tBRCA1 62 56 PR HGSC 6 HRD NA tBRCA2 NA 51 NA CR HGSC 7 HRD NA tBRCA2 NA 50 NA PR HGSC 8 HRD NA tBRCA2 NA UD NA PR HGSC 9 HRD HRD wt wt 79 52 PR HGSC 10 HRD NA wt NA 79 NA PR HGSC 11 HRD HRD wt wt 78 69 PR HGSC 12 HRD HRD wt wt 70 71 PR HGSC 13 HRD NA wt NA 70 NA PR HGSC 14 HRD HRP wt wt 51 34 PR HGSC 15 HRD HRP wt wt 49 41 PR HGSC 16 HRP HRP wt wt 31 33 PR HGSC 17 HRP HRP wt wt 31 28 SD HGSC 18 HRP HRP wt wt 30 19 PR LCNEC 19 HRP HRP wt wt 27 24 PR HGSC 20 HRP NA wt wt 27 UD SD HGSC 21 HRP HRP wt wt 25 28 PR HGSC 22 HRP HRP wt wt 16 15 PR HGSC 23 UD HRP NA wt UD 30 PR HGSC 24 UD NA NA NA UD NA PR HGSC HR: homologous recombination, HRD: homologous recombination deficient, HRP: homologous recombination proficient, UD: undeterminable, wt: wild type, CR: complete response, PR: partial response, SD: stable disease, HGSC: high grade serous carcinoma, LCNEC: large cell neuroendocrine carcinoma GIS scores frequently drop after chemotherapy in HRD tumors Genomic instability scores (GIS) can be influenced by chemotherapy. To explore this possibility, we compared GIS before and after NAC in 24 cases that underwent NAC followed by IDS. In unpaired comparisons, no significant difference in GIS was observed (Fig. 2 A). However, in paired comparisons, tumors classified as HRD based on pre-NAC samples showed a significant reduction in GIS after NAC, whereas HRP tumors did not exhibit significant changes (Fig. 2 B). Notably, two patients experienced a shift in HR status from HRD to HRP, with GIS values decreasing from 51 to 34 in one patient (#14) and from 49 to 41 in one patient (#15), crossing the threshold of 42 (Table 2, Fig. 2 B). BRCA signatures were consistent if available between pre- and post-NAC in all patients. These findings suggest NAC can lower GIS and alter HR status in BRCA wild-type (BRCAwt) HRD tumors. Discussion To the best of our knowledge, this is the first report comparing HR status based on the GIS and BRCA mutation status between pre- and post-NAC samples. In this study, we report three key findings regarding the impact of chemotherapy on the dynamics of GIS and HR status in ovarian cancer. First, we highlight the difficulty of obtaining high-quality samples—particularly post-NAC tissues—with sufficient DNA content for reliable GIS and BRCA mutation assessment. Previous reports have shown that the success rate of HR status determination exceeds 98% when tissue samples contain at least 30% tumor cells [ 12 ]. While small biopsy specimens obtained prior to NAC are generally sufficient, we encountered two cases—one from a colonoscopic biopsy and the other from a biopsy of a posterior vaginal vault lesion—in which HR status could not be determined due to insufficient tumor cellularity. The challenge of assessing HR status is even greater after NAC. In our study, all 24 patients had platinum-sensitive tumors that were judged to have responded reasonably well to initial chemotherapy. This corresponds to 63% of cases with prior chemotherapy, as shown in Fig. 1 , a rate that is also reported as 71% in previous studies [ 13 ]. In contrast, patients who respond poorly to chemotherapy often do not undergo IDS, thereby losing the opportunity to obtain tumor tissue—representing the remaining 37% of prior chemotherapy cases in Fig. 1 . Among the 24 post-NAC cases, referred to platinum-sensitive, 6 patients (25%) lacked sufficient tumor volume for HR status assessment due to a favorable response to chemotherapy. Notably, 4 of these 6 patients harbored tBRCA mutations, which are known to be associated with increased sensitivity to both chemotherapy and PARP inhibitors [ 14 , 15 ]. Although the remaining 2 cases were BRCA wild-type, one of which was determined with BRCAnalysis, the tumor had regressed to a degree that made HR status evaluation impossible. These findings are consistent with prior reports indicating that approximately 25–30% of tumors may completely regress following chemotherapy [ 16 ]. In one post-NAC case, GIS could not be assessed despite successful BRCA sequencing, potentially due to tissue degradation caused by chemotherapy or improper formalin-fixation process. In another case, HR status assessment was not performed because the tumor was deemed unresectable at IDS. Collectively, our findings underscore the challenges of obtaining adequate post-NAC tissue for HR status evaluation and highlight the importance of considering these limitations when planning treatment strategies. Second, we demonstrate that GIS significantly decreases after NAC in HRD tumors (p = 0.0046), but not in HRP tumors (p = 0.76). The most notable reduction was observed in HRD patient #9, with a GIS decline from 79 to 52. Given that chemotherapy reduces intratumor heterogeneity while sparing chemotherapy-resistant clones [ 17 ], we speculate that NAC selectively eliminates high-GIS, chemotherapy-sensitive cells, thereby enriching low-GIS, resistant clones. HGSOC is known to exhibit the highest GIS among cancer types [ 18 ], which may allow the pronounced decline observed in HRD tumors. Third, we observed a shift in HR status from HRD to HRP in two patients (Fig. 2 ). This change has important clinical implications, as it may influence eligibility for HRD-based maintenance therapies. In theory, post-NAC samples provide the most up-to-date representation of a tumor's HR status. However, if the post-NAC HR status is used for treatment decision-making, patients may lose the opportunity to receive maintenance therapies such as bevacizumab or olaparib, which are typically indicated for HRD tumors [ 5 , 19 , 20 ]. When HR status is assessed only after NAC, clinicians should be aware of the potential for GIS score reduction and the consequent shift in HR classification. In such scenarios, one option is to perform BRACAnalysis to detect germline BRCA mutations. According to the PAOLA-1 and CRISTALLE trials, the concordance rate between somatic and germline BRCA variants is approximately 74.6–76.4% [ 21 , 22 ], suggesting that germline BRCA status can be a valuable reference for determining eligibility for PARP inhibitor-based maintenance therapy. Alternatively, clinicians may consider using PARP inhibitors approved for HRP tumors, such as niraparib, which has shown efficacy irrespective of HR status [ 19 , 23 ]. One limitation of this study is the small sample size, which restricts the generalizability of our findings. Another limitation and point of concern of the study is that tBRCA2 tumors could not be compared due to the lack of residual tumors after chemotherapy. We aim to include a larger cohort in future studies to better understand the dynamics of GIS between pre- and post-NAC samples. Conclusions Our study demonstrates that NAC can reduce GIS scores and alter HR status preferentially in HRD tumors. Given the uncertainty of tissue availability after NAC and the potential shift from HRD to HRP status—which may limit eligibility for HRD-targeted maintenance therapies—we recommend performing HRD testing on tumor tissue prior to chemotherapy-induced modifications. Abbreviations NAC neoadjuvant chemotherapy IDS interval debulking surgery PFS progression-free survival OS overall survival HR homologous recombination HRD homologous recombination deficiencies HRP homologous recombination proficient GIS genomic instability score HGSOC high-grade serous ovarian carcinoma LCNEC large cell neuroendocrine carcinoma Declarations Ethics approval and consent to participate This retrospective study was approved by the Institutional Review Board of Ehime University Hospital (approval number 2212007). Written informed consent was obtained from participants whenever possible. For cases where obtaining individual consent was not feasible, an opt-out approach was applied in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan. The study was conducted in accordance with the principles of the Declaration of Helsinki. Consent for publication Not applicable Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Authors’ contributions I am grateful to all members of our medical department for their cooperation in treating patients. Dr. Murai provided a critical review and helped edit the manuscript. Funding This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. References World Cancer Research Fund. Cancer statistics: Ovarian cancer statistics. https://www.wcrf.org/cancer-trends/ovarian-cancer-statistics/. Accessed o1 Aug 2025. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. CA Cancer J Clin. 2018;68:284–96. González-Martín A, Harter P, Leary A, Lorusso D, Miller RE, Pothuri B, et al. Ann Oncol. 2023;34:833-48. 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Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Apr, 2026 Read the published version in Journal of Ovarian Research → Version 1 posted Editorial decision: Revision requested 07 Nov, 2025 Reviews received at journal 07 Nov, 2025 Reviewers agreed at journal 06 Nov, 2025 Reviews received at journal 06 Nov, 2025 Reviewers agreed at journal 04 Nov, 2025 Reviewers invited by journal 03 Nov, 2025 Editor assigned by journal 31 Oct, 2025 Submission checks completed at journal 31 Oct, 2025 First submitted to journal 25 Oct, 2025 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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07:09:29","extension":"xml","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":103961,"visible":true,"origin":"","legend":"","description":"","filename":"e1e979db8a354fd4962ecea8107388ea1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7947639/v1/b977f74b4ac465620c8a8cad.xml"},{"id":95845207,"identity":"476333e0-a0d2-4182-ae76-0d167b11f86c","added_by":"auto","created_at":"2025-11-13 14:48:45","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":112302,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7947639/v1/dce91b8672b30f873d5ecef6.html"},{"id":95845193,"identity":"78ee95c0-b482-4633-b6f8-a5a1918eb720","added_by":"auto","created_at":"2025-11-13 14:48:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":66777,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient flowchart.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 128 patients, 24 underwent NAC followed by IDS.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNAC: neoadjuvant chemotherapy, IDS: interval debulking surgery, PDS: primary debulking surgery, RT: radiation therapy.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7947639/v1/01a0d9ec6ede079695fac4d4.png"},{"id":96240760,"identity":"c8d11b15-aa09-4cee-870a-b3c53154b1ea","added_by":"auto","created_at":"2025-11-19 07:09:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":108748,"visible":true,"origin":"","legend":"\u003cp\u003eDynamics in GIS.\u003c/p\u003e\n\u003cp\u003eSamples with BRCA1/2 mutation are highlighted by pink dots and dashed red line shows the cut point at GIS =42.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(A) Unpaired group. Comparing GIS before and after NAC in 24 patients that underwent NAC followed IDS.\u003c/p\u003e\n\u003cp\u003e(B) Paired group by HRD and HRP based on pre-NAC.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHRD: homologous recombination deficiency, HRP: homologous recombination proficient, NAC: neoadjuvant chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7947639/v1/31b53fd4f0e5409f57e8e15f.png"},{"id":107927677,"identity":"520d9e26-c3ae-41d2-a56c-dd1e24eb9787","added_by":"auto","created_at":"2026-04-27 16:01:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":443152,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7947639/v1/41a36fb0-b174-468f-bb10-41bfd4e8afce.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers","fulltext":[{"header":"Background","content":"\u003cp\u003eOvarian, fallopian tube, and primary peritoneal cancers (collectively referred to as ovarian cancers) are the most lethal gynecological cancers in women and are the eighth leading cause of cancer-related death [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The overall survival rates of advanced ovarian cancers are 42% for stage III and 26% for stage Ⅳ [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Currently, the standard chemotherapy for newly diagnosed advanced ovarian cancer patients is platinum-based chemotherapy, either in combination with bevacizumab [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. While cytoreductive surgery followed by chemotherapy is the standard treatment, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) is considered for stage III and IV patients with poor surgical candidates, advanced disease, poor general condition, and surgical difficulty. Given the high recurrence rates, ovarian cancer patients often require additional treatment options following initial chemotherapy.\u003c/p\u003e\u003cp\u003eSince 2014, PARP inhibitors have become standard maintenance therapy, significantly improving progression-free survival (PFS) and/or overall survival (OS) in ovarian cancer patients. Initially developed as DNA repair inhibitors, PARP inhibitors were designed to induce synthetic lethality in tumors with BRCA mutations or homologous recombination (HR) deficiencies. However, their clinical indications now extend beyond BRCA mutations and HR deficiencies (HRD), as BRCA wild-type and HR-proficient (HRP) cancers may also benefit from PARP inhibitors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The indications for PARP inhibitors are complex and vary depending on the specific drug (e.g., olaparib, niraparib, rucaparib, talazoparib) and the tumor's HR status. For instance, based on the PAOLA-1 trial [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], the combination of bevacizumab and olaparib has been approved for HRD-associated advanced ovarian cancers in the first-line setting. Similarly, the SOLO1 trial led to the approval of olaparib for first-line treatment in patients with germline BRCA1/2 (gBRCA1/2) mutations [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Olaparib has also been approved for recurrent ovarian cancers regardless of HR status, based on the SOLO-2 and Study 19 trials, while niraparib received first-line approval irrespective of HR status through the PRIMA trial [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThus, HR status serves as a critical determinant in selecting post-chemotherapy maintenance treatment options for advanced ovarian cancers. Although various methods are available globally to determine HR status, the Myriad myChoice assay (Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] is the only companion diagnostic system approved in Japan. The myChoice assay defines HRD as either a genomic instability score (GIS) of \u0026ge;\u0026thinsp;42 or the presence of a tumor BRCA (tBRCA) mutation, while a GIS of \u0026lt;\u0026thinsp;42 is classified as HRP [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. GIS is considered stable and reflective of genomic instability scars, and a study reports that HR status was maintained between primary and recurrent lesions in 50 pairs of high-grade serous ovarian carcinoma (HGSOC) samples [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFor patients undergoing NAC followed by IDS, clinicians have two opportunities to obtain tumor samples: before and after NAC. In this study, we analyzed ovarian cancer patients who underwent NAC followed by IDS, focusing on both their tissues submitted for HR analysis. Our findings indicate that NAC can reduce GIS scores and alter HR status preferentially in HRD cases, and we highlight the frequent unavailability of tissue samples after NAC.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e2.1. Patients and study design\u003c/p\u003e\u003cp\u003eThis retrospective study was approved by the Institutional Review Board of Ehime University Hospital (approval number: 2212007). Written informed consent was obtained from participants whenever possible. For cases where obtaining individual consent was not feasible, an opt-out approach was applied in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan. The study was conducted in accordance with the principles of the Declaration of Helsinki. We enrolled a total of 128 patients with advanced ovarian, fallopian tube, and primary peritoneal cancers treated at Ehime University Hospital from November 2020 to April 2023. We obtained written informed consent from all patients before the enrollment. International Federation of Gynecology and Obstetrics (FIGO) 2014 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] was applied to stage the cancers. We then selected 24 patients who underwent NAC followed by IDS for further analysis.\u003c/p\u003e\u003cp\u003e2.2. Sample analysis\u003c/p\u003e\u003cp\u003eCancer tissues obtained at surgery or biopsy were submitted to Myriad myChoice\u0026reg; assay, and we obtained GIS and tBRCA mutation status. According to the guidance of HRD companion diagnostic test available from Myriad genetics, we defined HRD as either a GIS of \u0026ge;\u0026thinsp;42 or the presence of tBRCA mutation, while a GIS of \u0026lt;\u0026thinsp;42 was classified as HRP. A comparison of GIS change before and after NAC in each patient was carried out using the Welch paired t-test. A comparison of overall GIS change before and after NAC was carried out using the unpaired Student t-test. P values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered to indicate statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eClinical and pathological characteristics of the study population\u003c/h2\u003e\u003cp\u003eIn our cohort, 61 out of 128 ovarian cancer patients (47.6%) were classified as FIGO stage III or IV (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among these, 24 patients (39.3%) underwent platinum-based NAC followed by IDS and were included in further analyses (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age of the patients was 67 years (range: 49\u0026ndash;78). Diagnoses included ovarian cancer in 18 patients, fallopian tube cancer in 2 patients, and primary peritoneal cancer in 4 patients. FIGO stages were distributed as follows: IIIB (1 patient), IIIC (10 patients), IVA (4 patients), and IVB (9 patients). The histological type was high-grade serous ovarian carcinoma (HGSOC) in all but one patient, who had large cell neuroendocrine carcinoma (LCNEC). All patients received platinum-based chemotherapy, consisting of standard doses of carboplatin (AUC6) and paclitaxel (175 mg/m\u0026sup2;) on day 1 of a 21-day cycle. The median number of NAC cycles completed was 5 (range: 3\u0026ndash;7).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 1. Clinical and pathological characteristics. (n = 24)\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian age (range)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67 (49\u0026ndash;78)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOvary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFallopian tube\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePeritoneal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eⅢB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eⅢC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eⅣA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eⅣB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ehigh-grade serous carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLCNEC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian NAC cycle (range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNAC regimen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eNAC: neoadjyuvant chemotherapy, TC: paclitaxel\u0026thinsp;+\u0026thinsp;carboplatin, LCNEC: large cell neuroendocrine carcinoma\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePoor availability of tissue samples after NAC\u003c/h3\u003e\n\u003cp\u003eTo investigate the dynamics of HR status based on GIS and tBRCA mutation status, we attempted to obtain this information both pre- and post-NAC (Table\u0026nbsp;2). However, HR status was not determinable in 2/24 (8.3%) pre-NAC cases (patients #23 and #24) due to insufficient tumor tissue in the biopsy samples. There is one case (patient #8) who failed to obtain a GIS score, yet the case had tBRCA2 mutation status, which was insufficient to determine the HR status. At a post-NAC stage, HR status was unavailable or undeterminable in 8/24 (33%) cases (patients #4, #6\u0026ndash;8, #10, #13, #20, and #24). In detail, tBRCA mutation status was unavailable in 7/24 (28%) cases, and GIS scores were unavailable or undeterminable in 8/24 (33%) cases. The reasons are the following: pathological complete response (CR) in 2 cases (patients #6 and #24), insufficient tumor volume in IDS samples in 4 cases due to good response (patients #4, #7, #8 and #13), difficulty removing the tumor during IDS in 1 case (patient #10), and insufficient tumor tissue in 1 case (patient #20). As a result, paired HR status, pre- and post-NAC, were successfully obtained in only 15/24 (62.5%) cases. These findings highlight the challenges that clinicians face in acquiring tumor samples, particularly following NAC.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTable\u0026nbsp;2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e\u003cp\u003eDynamics of HR status pre- and post-chemotherapy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epatient #\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eHR status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eBRCA signature\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eGenomic Instability Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eClinical chemotherapy response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHistology\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epre\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003epost\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003epre\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003epost\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003epre\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003epost\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e73\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e62\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e67\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e63\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e63\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e49\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e63\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003etBRCA1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e62\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e56\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e51\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e50\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003etBRCA2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eUD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e79\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e52\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e79\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e78\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e69\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e70\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e71\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e70\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e51\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e49\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eLCNEC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eUD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eHRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ewt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eUD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eUD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHGSC\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cem\u003eHR: homologous recombination, HRD: homologous recombination deficient, HRP: homologous recombination proficient, UD: undeterminable, wt: wild type, CR: complete response, PR: partial response, SD: stable disease, HGSC: high grade serous carcinoma, LCNEC: large cell neuroendocrine carcinoma\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eGIS scores frequently drop after chemotherapy in HRD tumors\u003c/h3\u003e\n\u003cp\u003eGenomic instability scores (GIS) can be influenced by chemotherapy. To explore this possibility, we compared GIS before and after NAC in 24 cases that underwent NAC followed by IDS. In unpaired comparisons, no significant difference in GIS was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). However, in paired comparisons, tumors classified as HRD based on pre-NAC samples showed a significant reduction in GIS after NAC, whereas HRP tumors did not exhibit significant changes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). Notably, two patients experienced a shift in HR status from HRD to HRP, with GIS values decreasing from 51 to 34 in one patient (#14) and from 49 to 41 in one patient (#15), crossing the threshold of 42 (Table\u0026nbsp;2, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). BRCA signatures were consistent if available between pre- and post-NAC in all patients. These findings suggest NAC can lower GIS and alter HR status in BRCA wild-type (BRCAwt) HRD tumors.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first report comparing HR status based on the GIS and BRCA mutation status between pre- and post-NAC samples. In this study, we report three key findings regarding the impact of chemotherapy on the dynamics of GIS and HR status in ovarian cancer.\u003c/p\u003e\u003cp\u003eFirst, we highlight the difficulty of obtaining high-quality samples\u0026mdash;particularly post-NAC tissues\u0026mdash;with sufficient DNA content for reliable GIS and BRCA mutation assessment. Previous reports have shown that the success rate of HR status determination exceeds 98% when tissue samples contain at least 30% tumor cells [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. While small biopsy specimens obtained prior to NAC are generally sufficient, we encountered two cases\u0026mdash;one from a colonoscopic biopsy and the other from a biopsy of a posterior vaginal vault lesion\u0026mdash;in which HR status could not be determined due to insufficient tumor cellularity. The challenge of assessing HR status is even greater after NAC. In our study, all 24 patients had platinum-sensitive tumors that were judged to have responded reasonably well to initial chemotherapy. This corresponds to 63% of cases with prior chemotherapy, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, a rate that is also reported as 71% in previous studies [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In contrast, patients who respond poorly to chemotherapy often do not undergo IDS, thereby losing the opportunity to obtain tumor tissue\u0026mdash;representing the remaining 37% of prior chemotherapy cases in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among the 24 post-NAC cases, referred to platinum-sensitive, 6 patients (25%) lacked sufficient tumor volume for HR status assessment due to a favorable response to chemotherapy. Notably, 4 of these 6 patients harbored tBRCA mutations, which are known to be associated with increased sensitivity to both chemotherapy and PARP inhibitors [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although the remaining 2 cases were BRCA wild-type, one of which was determined with BRCAnalysis, the tumor had regressed to a degree that made HR status evaluation impossible. These findings are consistent with prior reports indicating that approximately 25\u0026ndash;30% of tumors may completely regress following chemotherapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In one post-NAC case, GIS could not be assessed despite successful BRCA sequencing, potentially due to tissue degradation caused by chemotherapy or improper formalin-fixation process. In another case, HR status assessment was not performed because the tumor was deemed unresectable at IDS. Collectively, our findings underscore the challenges of obtaining adequate post-NAC tissue for HR status evaluation and highlight the importance of considering these limitations when planning treatment strategies.\u003c/p\u003e\u003cp\u003eSecond, we demonstrate that GIS significantly decreases after NAC in HRD tumors (p\u0026thinsp;=\u0026thinsp;0.0046), but not in HRP tumors (p\u0026thinsp;=\u0026thinsp;0.76). The most notable reduction was observed in HRD patient #9, with a GIS decline from 79 to 52. Given that chemotherapy reduces intratumor heterogeneity while sparing chemotherapy-resistant clones [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], we speculate that NAC selectively eliminates high-GIS, chemotherapy-sensitive cells, thereby enriching low-GIS, resistant clones. HGSOC is known to exhibit the highest GIS among cancer types [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], which may allow the pronounced decline observed in HRD tumors.\u003c/p\u003e\u003cp\u003eThird, we observed a shift in HR status from HRD to HRP in two patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This change has important clinical implications, as it may influence eligibility for HRD-based maintenance therapies. In theory, post-NAC samples provide the most up-to-date representation of a tumor's HR status. However, if the post-NAC HR status is used for treatment decision-making, patients may lose the opportunity to receive maintenance therapies such as bevacizumab or olaparib, which are typically indicated for HRD tumors [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. When HR status is assessed only after NAC, clinicians should be aware of the potential for GIS score reduction and the consequent shift in HR classification. In such scenarios, one option is to perform BRACAnalysis to detect germline BRCA mutations. According to the PAOLA-1 and CRISTALLE trials, the concordance rate between somatic and germline BRCA variants is approximately 74.6\u0026ndash;76.4% [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], suggesting that germline BRCA status can be a valuable reference for determining eligibility for PARP inhibitor-based maintenance therapy. Alternatively, clinicians may consider using PARP inhibitors approved for HRP tumors, such as niraparib, which has shown efficacy irrespective of HR status [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOne limitation of this study is the small sample size, which restricts the generalizability of our findings. Another limitation and point of concern of the study is that tBRCA2 tumors could not be compared due to the lack of residual tumors after chemotherapy. We aim to include a larger cohort in future studies to better understand the dynamics of GIS between pre- and post-NAC samples.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study demonstrates that NAC can reduce GIS scores and alter HR status preferentially in HRD tumors. Given the uncertainty of tissue availability after NAC and the potential shift from HRD to HRP status\u0026mdash;which may limit eligibility for HRD-targeted maintenance therapies\u0026mdash;we recommend performing HRD testing on tumor tissue prior to chemotherapy-induced modifications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNAC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eneoadjuvant chemotherapy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIDS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003einterval debulking surgery\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eprogression-free survival\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eoverall survival\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehomologous recombination\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHRD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehomologous recombination deficiencies\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHRP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehomologous recombination proficient\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGIS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003egenomic instability score\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHGSOC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehigh-grade serous ovarian carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLCNEC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003elarge cell neuroendocrine carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the Institutional Review Board of Ehime University Hospital (approval number\u0026nbsp;2212007). Written informed consent was obtained from participants whenever possible. For cases where obtaining individual consent was not feasible, an opt-out approach was applied in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects in Japan. The study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed 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\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI am grateful to all members of our medical department for their cooperation in treating patients.\u003c/p\u003e\n\u003cp\u003eDr. Murai provided a critical review and helped edit the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Cancer Research Fund. Cancer statistics: Ovarian cancer statistics. https://www.wcrf.org/cancer-trends/ovarian-cancer-statistics/. Accessed o1 Aug 2025.\u003c/li\u003e\n\u003cli\u003eTorre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. CA Cancer J Clin. 2018;68:284\u0026ndash;96.\u003c/li\u003e\n\u003cli\u003eGonz\u0026aacute;lez-Mart\u0026iacute;n A, Harter P, Leary A, Lorusso D, Miller RE, Pothuri B, et al. Ann Oncol. 2023;34:833-48.\u003c/li\u003e\n\u003cli\u003eOnji H, Murai J. Cancer Sci. 2022;113:2943-51. \u003c/li\u003e\n\u003cli\u003eRay-Coquard I, Pautier P, Pignata S, P\u0026eacute;rol D, Gonz\u0026aacute;lez-Mart\u0026iacute;n A, Berger R, et al. N Engl J Med. 2019; 381:2416-28.\u003c/li\u003e\n\u003cli\u003eMoore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. N Engl J Med. 2018; 379:2495-505.\u003c/li\u003e\n\u003cli\u003eGonz\u0026aacute;lez-Mart\u0026iacute;n A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR. N Engl J Med. 2019;381:2391-402.\u003c/li\u003e\n\u003cli\u003eMyriad Genetics, MyChoice companion Diagnoitic test. 2025. https://myriad.com/genetic-tests/mychoicecdx-tumor-test/. Accessed 01 Aug 2025.\u003c/li\u003e\n\u003cli\u003eTelli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC,et al. Clin Cancer Res. 2016;22:3764-73.\u003c/li\u003e\n\u003cli\u003ePatel JN, Braicu I, Timms KM, Solimeno C, Tshiaba P, Reid J,et al. Br J Cancer. 2018;119:1060-6.\u003c/li\u003e\n\u003cli\u003eMutch DG, Prat J. Gynecol Oncol. 2014;133:401-4.\u003c/li\u003e\n\u003cli\u003eRomey M, Rodepeter F, Hattesohl A, Kaiser K, Teply-Szymanski J, Heitz F, et al. Mod Pathol. 2024;37:100445.\u003c/li\u003e\n\u003cli\u003eLiu YL, Zhou QC, Iasonos A, Filippova OT, Chi DS, Zivanovic O, et al. Int J Gynecol Cancer. 2020;30:1554-61. \u003c/li\u003e\n\u003cli\u003eXu Y, Chen YA, Wu Y, Saverimuthu A, Jadhav A, Bhuiyan R,et al. Front Oncol. 2024;14:1372482.\u003c/li\u003e\n\u003cli\u003eRay-Coquard I, Leary A, Pignata S, Cropet C, Gonz\u0026aacute;lez-Mart\u0026iacute;n A, Marth C; PAOLA-1/ENGOT-ov25 investigators. Ann Oncol. 2023;34:681-92.\u003c/li\u003e\n\u003cli\u003eB\u0026ouml;hm S, Faruqi A, Said I, Lockley M, Brockbank E, Jeyarajah A, et al. J Clin Oncol. 2015;33:2457-63. \u003c/li\u003e\n\u003cli\u003eTakaya H, Nakai H, Sakai K, Nishio K, Murakami K, Mandai M, et al. Gynecol Oncol. 2020;156:415-22.\u003c/li\u003e\n\u003cli\u003eMarquard AM, Eklund AC, Joshi T, Krzystanek M, Favero F, Wang ZC, et al. Biomark Res. 2015;3:9.\u003c/li\u003e\n\u003cli\u003eRichardson DL, Quintanilha JCF, Danziger N, Li G, Sokol E, Schrock AB, et al. Clin Cancer Res. 2024;30:4644-53.\u003c/li\u003e\n\u003cli\u003eLiu Y, Chen X, Lu H, Wu X, Liu X, Xu F, et al. Mol Diagn Ther. 2024;28:621-32.\u003c/li\u003e\n\u003cli\u003eCallens C, Vaur D, Soubeyran I, Rouleau E, Just PA, Guillerm E, et al. J Natl Cancer Inst. 2021;113:917-23.\u003c/li\u003e\n\u003cli\u003eOda K, Aoki D, Tsuda H, Nishihara H, Aoyama H, Inomata H, et al. Cancer Sci. 2023;114:271-80.\u003c/li\u003e\n\u003cli\u003eZhao Q, Bai L, Tan Y, Qie M. Front Oncol. 2024;14:1435029.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"homologous recombination deficiency (HRD), ovarian cancer, neoadjuvant chemotherapy, interval debulking surgery, genomic instability score (GIS)","lastPublishedDoi":"10.21203/rs.3.rs-7947639/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7947639/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eHomologous recombination (HR) status plays a pivotal role in the management of advanced ovarian, fallopian tube, and primary peritoneal cancers (collectively referred to as ovarian cancers), influencing treatment selection and response to PARP inhibitors. For patients undergoing neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS), clinicians have two opportunities to obtain tumor samples: before and after NAC. This study aimed to compare pre- and post-NAC samples to assess the impact of chemotherapy on HR status.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eBetween 2020 and 2023, 128 patients with ovarian cancer were treated at our institution. Among them, 24 underwent NAC followed by IDS. Tumor samples were analyzed using the Myriad myChoice\u0026reg; assay to determine genomic instability scores (GIS) and BRCA mutation status.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePost-NAC HR status was unavailable in 8 of 24 patients (33%) due to insufficient or degraded samples. Among the 15 patients with paired pre- and post-NAC samples, BRCA mutation status remained unchanged. However, GIS scores were significantly reduced in HR-deficient (HRD) tumors after NAC, whereas HR-proficient (HRP) tumors showed no significant change. Notably, two patients converted from HRD to HRP status, with GIS decreasing from 51 to 34 in one and from 49 to 41 in the other, crossing the HRD threshold of 42.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eNAC can reduce GIS and alter HR status in HRD tumors. Although post-NAC assessment may help refine treatment strategies after IDS, tissue availability is often limited. Moreover, conversion from HRD to HRP status following NAC may restrict eligibility for HR-targeted therapies.\u003c/p\u003e","manuscriptTitle":"Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-13 14:48:40","doi":"10.21203/rs.3.rs-7947639/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-07T19:43:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-07T13:38:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"39297743340399127454417017356473001826","date":"2025-11-07T02:00:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-06T08:04:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"104106046158964231678656549975399771839","date":"2025-11-04T18:23:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-03T20:17:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-31T13:59:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-31T12:38:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Ovarian Research","date":"2025-10-25T15:43:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ovarian-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jovr","sideBox":"Learn more about [Journal of Ovarian Research](http://ovarianresearch.biomedcentral.com)","snPcode":"13048","submissionUrl":"https://submission.nature.com/new-submission/13048/3","title":"Journal of Ovarian Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a36de789-a8a3-4a82-b590-71f6553ec0a3","owner":[],"postedDate":"November 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T16:00:43+00:00","versionOfRecord":{"articleIdentity":"rs-7947639","link":"https://doi.org/10.1186/s13048-026-02101-1","journal":{"identity":"journal-of-ovarian-research","isVorOnly":false,"title":"Journal of Ovarian Research"},"publishedOn":"2026-04-23 15:57:06","publishedOnDateReadable":"April 23rd, 2026"},"versionCreatedAt":"2025-11-13 14:48:40","video":"","vorDoi":"10.1186/s13048-026-02101-1","vorDoiUrl":"https://doi.org/10.1186/s13048-026-02101-1","workflowStages":[]},"version":"v1","identity":"rs-7947639","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7947639","identity":"rs-7947639","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}