Double Cancer Research Articles

The research progress on synchronous endometrial and ovarian carcinoma.

Synchronous endometrial and ovarian carcinoma (SEOC) is the most common combination of primary double cancer in the female reproductive system. The etiology and pathogenesis of SEOC remain unclear, and clinically, it is often misdiagnosed as metastatic cancer, affecting the formulation of treatment plans and prognosis for patients. This article provides a review of its epidemiology, pathological and clinical characteristics, risk factors, pathogenesis, diagnosis, treatment, and prognosis.

Dual blockade of CD47 and CD24 signaling using a novel bispecific antibody fusion protein enhances macrophage immunotherapy

CD47 and its receptor SIRPα act as a dominant anti-phagocytic, ‘don’t eat me’ signal. Recent studies reveal CD24 as a novel target for cancer immunotherapy by macrophages in ovarian cancer and breast cancer. However, whether simultaneous blockade of CD47 and CD24 by bispecific antibody may result in a potential synergy is still unclear. In the present study, we for the first time designed and developed a bispecific antibody fusion protein, PPAB001 for co-targeting CD47 and CD24. Data demonstrate that simultaneous blockade of CD47/SIRPα and CD24/Siglec-10 signaling by PPAB001 potently promoted macrophage phagocytosis of tumor cells. Compared to single CD47 or CD24-targeting agent, PPAB001 was more effective in inhibiting tumor growth in both mouse 4T-1 syngeneic and human SK-OV-3 xenogeneic tumor models. Mechanistically, we found that PPAB001 therapy markedly increased the proportion of tumor-infiltrating macrophages and upregulated IL-6 and TNF-α levels that were representative macrophage inflammatory cytokines. Notably, an increased ratio of M1/M2 in tumor-infiltrating macrophages in the mice treated with PPAB001 suggested that the dual blockade may promote the transition of macrophages from M2 to M1. Taken together, our data supported the development of PPAB001 as a novel immunotherapeutic in the treatment of CD47 and CD24 double positive cancers.

MO10-5 Germline and somatic whole exome sequencing identifies a novel candidate gene in double primary BCRA-associated cancers

MO10-5 Germline and somatic whole exome sequencing identifies a novel candidate gene in double primary BCRA-associated cancers

A Case of Double Primary Carcinoma was Accidentally Found During Operation: Hepatocellular Carcinoma and Appendiceal Mucinous Adenocarcinomas

Background: Synchronous double primary cancer of hepatocellular carcinoma (HCC) and appendiceal mucinous adenocarcinomas has not been reported. Liver metastasis of digestive tract tumors is so common that it is easy to ignore the existence of double primary cancer in the digestive system. The appendiceal malignant tumor itself is easy to be misdiagnosed or missed. For a better understanding of HCC and appendiceal mucinous adenocarcinomas, the information on our recent case has been summarized. Case Presentation: A 58-year-old man was admitted with repeated upper abdominal pain for one week. Imaging examination and liver biopsy pathology were diagnosed as hepatocellular carcinoma. Colonoscopy showed no obvious organic lesions in the terminal ileum and the whole large intestine. We had anatomical resection of the S5 and S6 segments of the liver. At the same time, two suspicious lesions in the right liver were ablated by microwave. But at the end of the operation, we accidentally found a hard mass about 3 cm × 3 cm in size at the end of the appendix. And the rapid pathological results showed appendiceal adenocarcinoma, so we had a right hemicolectomy. So far, the diagnosis of the patient was changed to synchronous double primary cancer consisting of HCC and appendiceal mucinous adenocarcinomas. Conclusion: It is the first time we have reported a case of synchronous double primary hepatic cancer consisting of HCC and appendiceal mucinous adenocarcinomas in the world. Due to the rarity and unspecific clinical features, it is extremely challenging to be diagnosed preoperatively. It requires a more comprehensive understanding of the patient's medical history, careful physical examination, and comprehensive exploration of the abdominal cavity during the operation to avoid missed diagnosis. Patients with HCC and appendiceal mucinous adenocarcinomas are generally associated with poor prognosis. It needs we put forward new countermeasures for the new question.

Multiple primary cancers: a case report and literature review

The fortuitous discovery of synchronous double primary cancers of the lung and stomach is relatively rare, but the discovery of triple primary cancers in one patient remains exceptional. The discovery of triple primary cancers in a single patient remains exceptional. This coexistence corresponds to the syndrome of multiple primary malignancies or multiple primary cancers (MPC). We present a case of synchronous association of squamous cell carcinoma of the lung and gastric adenocarcinoma with a history of mature squamous cell carcinoma of the larynx.

Successful delivery after in vitro fertilization-embryo transfer in a woman with metachronous primary cancer of ovary and endometrium: a case report

BackgroundThe appearance of malignancies at various times in the same individual, excluding metastases of the initial primary cancer, is termed multiple primary cancers. Double primary gynecological cancers cause inevitable damage to female reproductive function, and the preservation of fertility in such patients remains a challenging issue as relatively few cases have been reported. This case report provides management options for dual primary ovarian and endometrial cancers, including the choice of ovulation induction protocols, considerations during pregnancy and parturition, with the aim of providing assistance to clinicians.Case presentationWe report a case of a 39-year-old woman with primary infertility and a medical history of right-sided ovarian mucinous borderline tumor with intraepithelial carcinoma, left-sided ovarian mucinous cystadenoma and endometrial cancer, who successfully conceived with in vitro fertilization-embryo transfer (IVF-ET) after three different ovulation induction protocols. During her pregnancy, she was complicated by central placenta praevia with placental implantation and eventually delivered a healthy female infant by caesarean section at 33 gestational weeks.ConclusionsFor patients with double primary gynecological cancers who have an intense desire for fertility, the most appropriate oncological treatment should be applied according to the patient’s individual situation, and fertility preservation should be performed promptly. Ovulation induction protocol should be individualized and deliberate, with the aim of ensuring that the patient’s hormone levels do not precipitate a recurrence of the primary disease during induction of ovulation and maximizing fertility outcomes. In addition, the risk of postpartum hemorrhage due to placental factors cannot be neglected in such patients.

Analysis of clinicopathological features and prognosis of double primary cervical cancer and ovarian cancer based on SEER database.

Double primary cervical cancer and ovarian cancer refer to the simultaneous or successive appearance of cervical cancer and ovarian cancer in the same patient. Due to the low incidence, there are few relevant reports. Therefore, this study is the first population-based analysis of the clinicopathological features as well as the prognostic status of double primary cervical cancer and ovarian cancer. We look forward to providing a reference for future clinical diagnosis and treatment. In this study, 473 cases of double primary cervical cancer and ovarian cancer were collected from 1975 to 2019 through the SEER database. Double primary cancers were considered non-synchronous when they were diagnosed more than 6months apart and were classified as Group A. Double primary cancers were considered synchronous when the interval between diagnosis of the two tumors was less than or equal to 6months and was classified as group B. In this study, the incidence of double primary cervical cancer and ovarian cancer accounted for 0.39% of primary cervical cancer and 0.24% of primary ovarian cancer in the same period. 80% of patients developed second cancer within 107months of their first cancer being diagnosed. Compared with non-synchronous cancer, synchronous cancer is mainly characterized by simultaneous bilateral ovarian involvement and early clinical stage, but highly malignant, high lymph node metastasis rate, and poor prognosis. Most patients developed second cancer within 107months of their first cancer being diagnosed. Age at diagnosis, bilateral ovarian invasion, the interval between diagnoses, pathological type and stage of ovarian cancer, and grade of cervical cancer are important factors affecting survival, which still needs to be confirmed by more extensive studies in future.

A case of synchronous double cancers consisting of maxillary gingival carcinoma and intraductal papillary mucinous carcinoma, invasive: case report

BackgroundThe development of synchronous multiple primary cancers is one of the major causes of death in patients with head and neck cancer. Herein, we report a case of synchronous intraductal papillary mucinous carcinoma (IPMC), invasive in a patient with maxillary gingival carcinoma.Case presentationA 73-year-old female visited our hospital complaining of a mass on the left side of the maxillary gingiva. Intraorally, an exophytic tumor, 50 × 25 mm in size, was found on the gingiva of the left maxillary posterior, and a diagnosis of squamous cell carcinoma was revealed by cytology. Emission tomography/ computed tomography with 18 Fluorodeoxyglucose-Positron (18FDG- PET/ CT) showed increased accumulation in the left maxillary gingiva, the left side of cervical lymph nodes, and the main pancreatic duct. The pancreatic ductal tumor was performed the biopsy at esophagogastroduodenoscopy (EGD) and resulted in a pathological diagnosis of IPMC, invasive. The patient was diagnosed as synchronous double primary cancers consisting of maxillary gingival carcinoma cT4aN2bM0 and IPMC, invasive cT3N0M0. She refused radical treatment, and died 11 months later.Conclusion18FDG- PET/ CT, EGD and multidisciplinary approach is required for the detection and determining the treatment strategy of synchronous double primary cancers.

Limitation of PET/CT for screening of synchronous upper gastrointestinal cancer in oral cancer patients

ObjectivePatients with squamous cell carcinoma (SCC) of the head and neck including the oral cavity have a high risk of upper gastrointestinal cancer, especially esophageal cancer. Synchronous upper gastrointestinal cancers affect the field of radiation or surgery, and undetected double cancer can cause poor prognosis. The purpose of this retrospective study was to evaluate the diagnostic performance of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting synchronous upper gastrointestinal cancer at the initial staging of oral cancer patients. MethodsBetween September 2006 and August 2021, 804 newly diagnosed oral squamous cell carcinoma patients who undergo esophagogastroduodenoscopy (EGD) and FDG-PET/CT at the initial staging were enrolled in this study. The incidence of synchronous upper gastrointestinal cancer in EGD screening at the initial staging of oral cancer was retrospectively calculated. Furthermore, we evaluated the diagnostic performance of FDG-PET/CT for screening of synchronous upper gastrointestinal cancer in oral cancer patients. ResultsThe incidence of synchronous upper gastrointestinal cancer in EGD screening at the initial staging of oral cancer was 4.2% (34/804 patients). Of 34 oral cancer patients with synchronous upper gastrointestinal cancer, 26 (76.5%) had both smoking and drinking habits. The sensitivity, specificity, accuracy, false-negative rate, false-positive rate, positive predictive value, and negative predictive value of FDG-PET/CT for synchronous upper gastrointestinal cancer were 44.1%, 99.6%, 97.3%, 55.9%, 0.4%, 83.3%, and 97.6%, respectively. ConclusionsBecause PET/CT cannot sufficiently detect synchronous upper gastrointestinal cancer in oral SCC patients, EGD screening before the treatment may be suitable for the high-risk oral SCC patients.

Abstract PR008: Molecular determinants of prostate cancer lineage plasticity

Abstract Androgen deprivation therapy (ADT) has been an effective treatment for advanced prostate cancer (PCa) for decades because PCa retains the lineage specific dependence of normal prostate tissue on androgen receptor (AR) signaling. Unfortunately, nearly all patients will progress through ADT with castrate resistant prostate cancer (CRPC). CRPC is typically associated with reactivation of AR signaling despite ADT. However with widespread clinical deployment of potent AR signaling inhibitors, an increasing fraction of CRPCs (~20) are now observed to lose AR signaling activity and show gene expression patterns consistent with alternative lineage states. These lineage variants share clonal origin with the pre-existing adenocarcinoma, so some PCa cells have sufficient plasticity to reprogram to an AR independent lineage state like neuroendocrine prostate cancer (NEPC) that is recalcitrant to available therapies. The molecular determinants of prostate cancer lineage plasticity are incompletely defined, and this knowledge gap has hindered development of diagnostic and therapeutic approaches necessary to identify and treat prostate cancer lineage plasticity. We present results from experiments testing the contribution of EZH2 and NOTCH signaling to prostate cancer lineage plasticity and NEPC reprogramming. EZH2 expression is elevated in advanced PCa, particularly NEPC, suggesting it drives lineage reprogramming. However, using genetically engineered mice and organoids we find that EZH2 is not required for NEPC reprogramming that occurs in some PCa cells in the absence of the RB1 and TP53 tumor suppressor genes. EZH2 deficiency does alter multi-lineage prostate cancer plasticity, biasing development towards lineage variants observed clinically including amphicrine and double negative prostate cancer. In contrast, data from clinical specimens indicates NOTCH signaling activity declines in NEPC compared to AR+ CRPC. NOTCH signaling suppresses NEPC development in both organoids and genetically engineered mice, and loss of NOTCH signaling is required to maintain the NEPC lineage state. Constitutive NOTCH signaling biases PCa development towards unique lineage variants including AR positive metastatic PCa with luminal differentiation. These results identify EZH2 and NOTCH signaling as molecular determinants of PCa lineage plasticity and NEPC reprogramming with implications for ongoing efforts to target these molecules for PCa therapy. Citation Format: Kristine Wadosky, Sheng-Yu Ku, Yanqing Wang, Xiaojing Zhang, Jie Wang, Jianmin Wang, Himisha Beltran, David W. Goodrich. Molecular determinants of prostate cancer lineage plasticity [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR008.

Feasibility and clinical utility of cancer whole-genome sequencing in adult solid tumors.

e15055 Background: As sequencing costs decrease, whole-genome sequencing (WGS) is expected to be utilized in actual cancer patient care. However, there is insufficient evidence that WGS can be applied to the real-world cancer patient care, and how it can help in the diagnosis and treatment process. Methods: This prospective cohort study was designed to evaluate the feasibility and clinical utility of WGS in adult solid cancer care at a tertiary hospital. All solid cancer patients who were scheduled to undergo biopsy or surgery for diagnosis or treatment were eligible for the study. Either fresh or formalin-fixed paraffin-embedded tissue with match peripheral blood were obtained. Tumors were sequenced to depth of 40x, and WGS data were curated by Genome Insight Inc. The WGS reports were provided to clinician through a web-based, user-browsable reporting system in real time. Results: 97 patients were enrolled between Sep 2022 and Jan 2023. Besides 10 QC failed cases, 87 patients were provided WGS reports. Median turn-around-time was 14 day (range 12-23). The clinical utility of WGS was evaluated in 77 cancer patients, excluding 10 cases with estimated cancer cell fraction less than 15%. 31 patients (40.3%) had more than one actionable alteration targeted by on-label drugs. 49 patients (63.6%) also had more than one actionable alteration targeted by either on-label or off-label drugs. In selected cases (N = 6), WGS could suggest the diagnosis for cancer of unknown origin or the revision of pathologic diagnosis that was regarded as a double primary cancer into a metastasis of a single cancer. By providing information of total mutation counts, whole-genome-wide mutational signature analysis, copy number variation with high accuracy, germline alterations, detection of homologous recombination deficiency, and presence of loss-of-heterozygosity, WGS could further refine the actionable mutations in 39% cases, and estimate the etiology of cancer (genomic or environmental) or to determine hereditary or sporadic cancer in 60% cases. In 90% cases, WGS demonstrated clinical utility with supporting diagnosis, informing carcinogenesis, or annotating actionable alterations. Conclusions: WGS was applicable in real-world cancer care. WGS demonstrated clinical utility in the diagnosis and treatment of adult cancer patients. Clinical trial information: KCT0008118 . [Table: see text]

Clinical characteristics and prognostic nomogram analysis of patients with dual primary cancers with first gastric cancer: a retrospective study in China.

With the improvement in diagnosis and treatment of gastric cancer (GC), the survival time of patients has been gradually prolonged. However, these survivors are at increased risk for other diseases, including second primary cancers (SPCs). Currently, there remain few central studies concerning double primary cancers with first gastric cancer (DPCFGC). Thus, this study aimed to investigate these patients' clinical characteristics and perform prognostic nomogram analysis. The clinical data of 78 DPCFGC patients were retrospectively collected and analyzed through the hospital electronic medical record system. Univariate and multivariate Cox regression analyses were performed to screen independent risk factors, based on which the prognostic nomogram was further constructed and validated using the R software package. Finally, Kaplan-Meier curves were plotted to explore the association of overall survival (OS) with prognostic factors and the model. The prevalence of DPCFGC was 0.86%, of which the proportions of synchronous and metachronous patients were 47.44% and 52.56% , respectively; 65.38% (51/78) and 34.62% (27/78) of patients were male and female, respectively. The median age at GC and SPC diagnosis was 63 and 65 years, respectively, and 52.57% of GC patients developed SPCs within 1 year. The top three SPCs were in the esophagus (19.24%), colon (16.67%), and rectum (15.39%). The most common features of GC and SPCs were adenocarcinoma, poorly and moderately differentiated histology, and pathological stages I and II. The radical resection rate of GC was significantly lower in synchronous patients than in metachronous patients (45.94% vs. 100.00%, P < 0.001), but no significant difference was noted in the radical resection rate of SPCs (35.13% vs. 46.34%, P = 0.315). The OS of DPCFGC patients was 31.03 ± 4.14 months. The pathological stage of GC and SPCs, whether to operate for GC, and diagnostic interval were independent risk factors. The predictive efficacy of the prognostic nomogram for 1-, 2- and 3-year OS in DPCFGC patients was 0.922, 0.935 and 0.796 , respectively, with good consistency and clinical applicability. The OS was significantly lower in the high-risk group than in the low-risk group. During follow-up, clinicians should attach great importance to the screening of GC survivors, especially at early stage in older men within 1 year after diagnosis, and be alert to the possibility of occurrent digestive system malignancies. The nomogram constructed in this study can provide a theoretical basis for the early clinical development of individualized treatment plans.

Abstract 129: Determine the genetic similarity of synchronous endometrial and ovarian cancers with variants in polyguanine sequences

Abstract Endometrial and ovarian cancers are both fearsome gynecological diseases with high mortality rates worldwide. Due to their histological similarity, it is still a clinical challenge to distinguish between double primary cancer (DPC) and metastasis cancer (MC) in synchronous endometrial and ovarian cancers in which the latter represents a poor prognostic outcome. Clinically, the standard procedure for examining DPC and MC relies on their morphology and histopathology; however, showing poor accuracy even under explicating criteria. Here, we attempt to utilize indel variants within polyguanine (polyG) sequences to generate genetic distances of synchronous endometrial and ovarian tumors to normal tissue in a patient and then calculate the correlation coefficient for them. Polyguanine sequences are hypermutable guanine repeats that acquire insertion or deletion at a high incident rate (mutation rate: ~10-6 - 10-4; ~1000 folds higher than unique sequence) and, therefore, could serve as a very rich resource for comparing the genetic similarity between samples. The correlation between selected clinical variables, e.g., disease-free survival and the described correlation coefficient is then calculated to test whether this protocol can serve as an optimal tool for distinguishing between DPC and MC. We have assembled a cohort of 39 patients with synchronous endometrial and ovarian cancers in which pathologists cannot determine the relationship between endometrial and ovarian cancer in 23 of them. Preliminarily, we have collected DNA from formalin-fixed paraffin-embedded (FFPE) specimens and completed polyG genotyping for four of them. Indel variants, both insertions and deletions, are rich in all cases indicating the approach is technically rigid for this purpose even with FFPE specimens. Subsequently, we evaluate the similarity between endometrial and ovarian cancer by calculating Spearman's correlation with the genetic distances obtained from polyG genotyping. As the result of preliminary cases, we observe the correlation coefficient spreading between -0.14 to 0.95, implying this methodology can determine the genetic similarity between endometrial and ovarian tumor in a case and, therefore, could be a potential tool to supplement the current observation-based approach in the clinic. Our next step is to correlate the correlation coefficients with meaningful clinical variables once we complete genotyping the entire cohort. We anticipate this approach could provide additional information to distinguish DPC and MC and therefore benefit the patients. Citation Format: Yu-Yi Huang, Pei-Chi Cheng, Ching Hsu, Yung-Ming Jeng, Lin-Hung Wei, Wei-Ting Hung. Determine the genetic similarity of synchronous endometrial and ovarian cancers with variants in polyguanine sequences [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 129.

Abstract 6307: A novel pegylated bispecific antibody-drug conjugate (P-BsADCpb-adc) targeting cancers co-expressing PD-L1 and CD47

Abstract ADCs have demonstrated improved efficacy and target selectivity comparing to the non-specific small molecule cytotoxicity drugs in cancer treatment. Yet, in solid tumor therapies, effort for further improvement of efficacy and safety has been hindered by the poor tumor penetration of conventional IgG based ADC, low internalization efficiency, undesired efflux of ADC from tumor cells, narrow therapeutic window due to the on-target/off tumor and Fc induced toxicity, etc. To address those issues, we previously reported that the compound JY201, a Polyethylene Glycol (PEG)-based bispecific ADC (P-BsADC) targeting two epitopes of Her2, demonstrated advantages in tumor penetration, internalization efficiency, lysosome trafficking, no Fc related toxicity, and better efficacy in tumor inhibition than transtuzumab deruxtecan (Ds-8201). In this study, we reveal another novel pegylated P-BsADC (JY207) formed by site-specific conjugation of a bispecific single chain fusion protein targeting PD-L1 and CD47 with PEG-MMAE (a pegylated cytotoxic payload MMAE). As expected, the compound JY207 retains all the advantages that JY201 possesses. Furthermore, JY207 does not bind to human red blood cells, but preferentially binds to CD47/PD-L1 double positive tumor cells, thus reduces the possibility of on-target toxicities. In vitro cytotoxicity studies showed that JY207 has strong potencies in CD47/PD-L1 double positive tumor cells, while showing almost no killing effect to CD47 or PD-L1 single positive tumor cells. In CDX models and a PDX model of transplanted tumor tissues from lung cancer patients, the compound demonstrated excellent tumor inhibition at low doses. In an in vitro plasma stability test, JY207 displays high stability in cynomolgus monkey and human serums. Preliminary repeated-dosing toxicological study has found the maximum tolerated dose of JY207 in CD47/PD-L1 double transgenic mice is 50mg/kg. In vivo pharmacokinetics and toxicological studies of JY207 are being conducted in cynomolgus monkeys and are expected to show desirable results. All those findings in this study warrant JY207 as a promising candidate for the clinical development for patients with CD47/PD-L1 double positive cancers. Citation Format: Shumin Liu, Weidong Lyu, Shuqiang Yin, Yang Lei, Qiudong Zhuo, Liling Zheng, Bin Sun, Shuangyu Tan, Lidong Jiang, Teng Zhang, Bo Gao, Rui Xu, Dechang Huang, Yong Li, Zibin Wu, David Wu, Yvonne (Yu) Wen. A novel pegylated bispecific antibody-drug conjugate (P-BsADCpb-adc) targeting cancers co-expressing PD-L1 and CD47. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6307.

Characteristics and survival analysis of breast cancer survivors with metachronous double primary cancers: a retrospective cohort study.

Breast cancer (BC) is the most frequently diagnosed malignancies in females, and its incidence has increased dramatically recently. Clinical studies have shown that BC patients are developing double primary cancers more frequently than by chance, and the prognosis has changed greatly. Previous articles rarely mentioned metachronous double primary cancers in BC survivors. Thus, further analysis of the clinical characteristics and survival differences may provide valuable information in BC survivors. In this study, we retrospectively analyzed 639 cases of double primary cancers in BC patients. Cox univariate and multivariate regression analyses of clinical factors of overall survival (OS) were performed in patients with double primary cancers when breast cancer was the primary tumor to assess the correlation between clinical factors and OS in these patients with double primary cancers. Among the double primary cancer patients, BC was the most frequent first primary cancer. In terms of numbers, thyroid cancer was the most common type of double primary cancer among BC survivors. Patients had a younger median age when BC occurred as the first primary cancer rather than the second primary cancer. The total mean time interval between the onset of double primary tumors was 70.8 months. With the exception of the thyroid and cervical cancer, the incidence of second primary tumors was <60% within 5 years. However, the incidence was >60% within 10 years. The mean OS of double primary cancer patients was 109.8 months. Additionally, patients who had thyroid cancer as their second primary cancer had the highest 5-year survival rate, followed by cervical, colon, and endometrial cancer, while patients who had lung cancer as their second primary cancer had the lowest 5-year survival rate. OS risk of BC survivors with second primary cancers was significantly associated with age, menopause status, family history, tumor size, lymph node metastasis, and human epidermal growth factor receptor 2 (HER2) status. The identification of double primary cancers in earlier stages could play a critical role in guidance and lead to better outcomes. A prolonged follow-up examination period for BC survivors is needed to provide better guidance and treatments.

Abstract P3-03-26: Osteopenia and osteoporosis in women with breast cancer in Taiwan: single center retrospective data

Abstract Purpose: Osteopenia and osteoporosis are commonly encounter in elder women. One third of women elder than fifty years suffer a fracture second to osteoporosis around the world. Standard treatments for breast cancer such as chemotherapy or hormonal therapy may increase the risk of both osteopenia and osteoporosis. Premenopausal women treated with standard adjuvant chemotherapy frequently develop ovarian failure, or early menopause, which is associated with accelerated bone loss. Trabecular bone score (TBS), an index extracted by DXA that provides an indirect measurement of bone axial microarchitecture. In addition to the BMD, TBS are warranted to improve the prediction of fracture risk at the individual level. However, due to regulations of National Health Insurance in Taiwan, data are limited on the incidence of osteopenia and osteoporosis in women with breast cancer in Taiwan. In this study, we investigated the proportion of osteopenia and osteoporosis in women with breast cancer in Taiwan. Materials and Methods: There were enrolled 201 female who diagnosed with breast cancer between May 2019 and December 2020 in this retrospective study. Patients with bone metastasis (n=11) and double cancer(n=3) were excluded. All patients received dual energy X-ray absorptiometry (DXA) at least once, including bone mineral density (BMD), T-score (spine and total hip) and trabecular bone score (TBS) data. The data were retrospectively analyzed baseline age, BMD, breast cancer type, aromatase inhibitors (AIs) usage status by Kruskal-Wallis test. Results: Basing on the lowest T-score from measurements at the spine or total hip, 58.8% (n=110) of osteopenia (-2.5≤T←1) and 27.8%(n=52) of osteoporosis (T←2.5) were identified in women with breast cancer (figure1). Statistics significance was noted in patients’ age and BMI between three groups. There was no difference in bone mineral density according to breast cancer subtype. (table 1) Patients who ever use aromatase inhibitors (n=90) had lower BMD (T=-2.14) and trabecular bone score (TBS=1.3) than non-AI group (n=97, T=-1.84, TBS=1.34). (figure 2) (table 2) Conclusions: According to Taiwan’s NHI sampling data from 1999 to 2001, the averaged prevalence of osteoporosis in those aged ≥50 years was 11.35% for women. Breast cancer survivors are at higher risk for osteopenia and osteoporosis compared to cancer-free women in Taiwan. Aromatase inhibitors (AIs) group had lower BMD and TBS (p&amp;lt; 0.05). In our study, forty percent of TNBC patients diagnosed osteoporosis, which is compatible with increased bone loss due to chemotherapy-induced ovarian failure. Therefore, clinicians should be aware not only of AI-associated bone loss but also of patients who ever accepted long-term chemotherapy. A normal range for TBS values in postmenopausal women has been proposed: a TBS of ≥1.350 is considered normal; a TBS between 1.20 and 1.35 is considered consistent with partially degraded microarchitecture, and a TBS of ≤ 1.200 defines degraded microarchitecture. In our study, mean TBS in women with breast cancer (n=187) is 1.32. Further research is needed to determine the validity of cut-points for guiding treatment decisions. Figure 1. Inclusion/exclusion criteria and flow chart Figure 1. Inclusion/exclusion criteria and flow chart Table 1 Figure 2. Aromatase inhibitors group had lower BMD and Trabecular bone score Figure 2. Aromatase inhibitors group had lower BMD and Trabecular bone score Citation Format: Chia-Hua Liu, Chih-Chiang Hung, I-Chen Tsai. Osteopenia and osteoporosis in women with breast cancer in Taiwan: single center retrospective data [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-26.

A case of multidisciplinary treatment for a synchronous double cancer of squamous cell carcinoma of the tongue and malignant lymphoma

A case of multidisciplinary treatment for a synchronous double cancer of squamous cell carcinoma of the tongue and malignant lymphoma

Diverse genetic spectrum among patients who met the criteria of hereditary breast, ovarian and pancreatic cancer syndrome.

Genetic high-risk assessment combines hereditary breast, ovarian and pancreatic cancer into one syndrome. However, there is a lack of data for comparing the germline mutational spectrum of the cancer predisposing genes between these three cancers. Patients who met the criteria of the hereditary breast, ovarian and pancreatic cancer were enrolled and received multi-gene sequencing. We enrolled 730 probands: 418 developed breast cancer, 185 had ovarian cancer, and 145 had pancreatic cancer. Out of the 18 patients who had two types of cancer, 16 had breast and ovarian cancer and 2 had breast and pancreatic cancer. A total of 167 (22.9%) patients had 170 mutations. Mutation frequency in breast, ovarian and pancreatic cancer was 22.3%, 33.5% and 17.2%, respectively. The mutation rate was significantly higher in patients with double cancers than those with a single cancer (p<0.001). BRCA1 and BRCA2 were the most dominant genes associated with hereditary breast and ovarian cancer, whereas ATM was the most prevalent gene related to hereditary pancreatic cancer. Genes of hereditary colon cancer such as lynch syndrome were presented in a part of patients with pancreatic or ovarian cancer but seldom in those with breast cancer. Families with a history of both ovarian and breast cancer were associated with a higher mutation rate than those with other histories. The mutation spectrum varies across the three cancer types and family histories. Our analysis provides guidance for physicians, counsellors, and counselees on the offer and uptake of genetic counseling.

Clinicopathologic Characterization of Double PIK3CA Mutated Advanced Breast Cancer: A Retrospective Cohort Study from a Single Institution

Objectives: We aimed to characterize the clinicopathologic and molecular features of double PIK3CA mutated advanced breast cancer in a retrospective cohort study. Methods: This retrospective study included 196 advanced breast cancer patients who had the Oncomine next generation sequencing analysis. The clinicopathologic parameters were recorded for each individuals including age, tumor type, grade, ER, PR, HER2, and recurrence free survival. Results: PIK3CA mutations were detected in 77.5% (152/196) of advanced breast cancer patients, 129 (84.8%) of which contained single mutations, 20 (13.1%) of which contained double mutations, and 3 (2%) of which contained triple mutations. Double PIK3CA mutated tumors were mostly seen in postmenopausal women, had lower combined histologic grade, and were enriched in hormone receptor positive human epidermal growth factor receptor negative (HR+/HER2-) disease. Double PIK3CA mutations were more frequently associated with concurrent mutations of ESR1 (p=0.017) and ARID1A (p=0.054) compared to single PIK3CA mutations. No significant progression free survival differences were observed between PIK3CA mutated and wild-type groups and between double and single PIK3CA mutated groups when applied to all patients or HR+/ HER2- patients. Conclusion: Double PIK3CA mutated advanced breast cancer have similar clinicopathologic features as single mutated ones but demonstrate unique molecular features.

Characteristics and survival analysis of breast cancer survivors with metachronous double primary cancers: a retrospective cohort study

Jianli Ma, Jinlu Wang, Xiuli Wang, Rui Li, Xingjian Niu, Yue Yang, Xudong Yang, Lei Yin, Yiran Wang, Han Zhang, Ruixue Shui, Cuiying Zhang, Ying Song