Cancer Research and Treatment

Evaluating the Effects of Mindfulness-Based Self-Help via an OTT Platform on Breast Cancer Patients Undergoing Radiotherapy: A Prospective Non-Randomized Controlled Trial: Hyejo Ryu, Si Nae You, Sohee Oh, Bora Kim, Jeong-Hyun Kim, In Ah Kim; Received October 1, 2024 Accepted November 20, 2024 Published online November 25, 2024; DOI: https://doi.org/10.4143/crt.2024.955 [Accepted]

Abstract PDF: Purpose
Previous research showed the benefits of mindfulness meditation on the mental health and quality of life of breast cancer patients. Traditionally, these programs relied on in-person interactions, but the COVID-19 pandemic necessitated alternative delivery methods. This study evaluated the effectiveness and feasibility of a mindfulness-based self-help (MBSH) program via Netflix for breast cancer patients undergoing radiotherapy.
Materials and Methods
This prospective non-randomized controlled study assigned patients to a control or MBSH group based on age and preference. The MBSH group watched episodes of "Headspace Guide to Meditation" on Netflix and practiced guided meditation at least twice per week for four weeks. Participants completed questionnaires assessing depression, anxiety, stress, insomnia, mindfulness, mental adjustment to cancer, and quality of life at weeks 0 and 8. Data were analyzed using a two-way repeated measures ANOVA.
Results
Ninety-six patients participated, with 84 eligible for final analysis (44 control, 40 MBSH). Intention-to-treat analysis revealed a significant improvement in depression (f=4.306, p=0.041). Half of the experimental group (n = 20) adhered to the study protocol. At week 8, the experimental group showed significant improvement compared to the control group in cognitive avoidance (f=8.530, p=0.005) and positive attitude (f=5.585, p=0.021), both indicative of adaptive coping strategies.
Conclusion
This study firstly investigated the effect and feasibility of a Netflix-based MBSH program for breast cancer patients undergoing radiotherapy. Findings suggest MBSH on Netflix can improve mental health and adaptive mental adjustment, highlighting the potential of self-help mindfulness interventions to enhance the well-being of cancer patients and need for further research.

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Estimation of Population Attributable Fraction by Hormone and Reproductive Factors on Female Cancer in the Republic of Korea, 2015 to 2030: Youjin Hong, Soseul Sung, Woojin Lim, Sungji Moon, Kwang-Pil Ko, Jung Eun Lee, Inah Kim, Sun Ha Jee, Sun-Seog Kweon, Min-Ho Shin, Sangmin Park, Seung-Ho Ryu, Sun Young Yang, Jeongseon Kim, Sang-Wook Yi, Yoon-Jung Choi, Jeong-Soo Im, Hong Gwan Seo, Sue K. Park; Received July 26, 2024 Accepted November 18, 2024 Published online November 19, 2024; DOI: https://doi.org/10.4143/crt.2024.707 [Accepted]

Abstract PDF: Purpose
Population attributable fractions (PAFs) for hormone and reproductive factors have been estimated in several countries. IARC designated as Group 1 and Group 2A carcinogen for hormone factors in breast, ovarian, endometrial and uterine cervix cancer. This study aimed to estimate the PAFs of hormone/reproductive factor attributed to cancer incidence and deaths in Korean women and projected trends from 2015 to 2030.
Materials and Methods
The PAF was estimated with using the 2005 standardized prevalence rates and 2020 incidence and deaths with a 15-year latency. Based on the Levin’s formula, prevalence rates were calculated using the Korea National Health and Nutrition Examination Survey (KNHANES) and the relative risks (RRs), which were the risk of selected female cancer associated with oral contraceptive, hormone replacement therapy and duration of breastfeeding, were estimated from the meta-analysis of studies performed in Korean women population. Studies based on the Asian and Global populations were calculated as a sensitivity analysis.
Results
The estimation PAFs for hormone was 1.02% with 1,192 cases and reproductive was 2.67% with 3,112 cases. Moreover, 0.40% (125 deaths) and 1.09% (342 deaths) in female-related cancer deaths in order. EP combined HRT accounted the most proportion in hormone factors and breastfeeding in reproductive factors. Also, the breast cancer had the highest percent in both hormone and reproductive factors.
Conclusion
Through this study, 1.02% and 2.67% of female-related cancer incidence will be reduced by encouraging avoiding the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) and breastfeeding for more than 6 months in reproductive factors. Additionally, among four selected female cancers in this study, breast cancer was observed to be a significant level of prevention.

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Kinect-Based Mixed Reality Exercise Program Improves Physical Function and Quality of Life in Breast Cancer Survivors: A Randomized Clinical Trial: Byunggul Lim, Xinxing Li, Yunho Sung, Parivash Jamrasi, SoYoung Ahn, Hyejung Shin, Wook Song; Received August 8, 2024 Accepted October 28, 2024 Published online October 30, 2024; DOI: https://doi.org/10.4143/crt.2024.758 [Accepted]

Abstract PDF: Purpose
Exercise is an effective non-pharmacological approach for alleviating treatment-related adverse effects and enhancing physical fitness in breast cancer survivors. A Kinect-based mixed reality device (KMR), with real-time feedback and user data collection, is an innovative exercise intervention for breast cancer survivors. This study aimed to investigate the effect of KMR exercise program on quality of life (QOL) and physical function in breast cancer survivors.
Materials and Methods
Seventy-seven participants were randomly assigned to either the KMR exercise group or home stretching group with an 8-week intervention. Physical function (shoulder range of motion [ROM], body composition, aerobic capacity, and hand grip strength) was evaluated before and after the intervention period. Participants completed questionnaires such as the Disabilities of the Arm, Shoulder, and Hand (DASH), Functional Assessment of Cancer Therapy-Breast, and International Physical Activity Questionnaire (IPAQ) to assess upper extremity disabilities, QOL, and physical activity levels.
Results
Significant group-by-time interaction was found for flexion of the operated arm (154.3±12.5 to 165.8±11.2), and the non-operated arm (158.2±13.8 to 166.5±12.2), abduction of the non-operated arm (154.8±31.6 to 161.1±28.1), and adduction of the operated arm (46.5±9.1 to 52.6±7.2). Significant improvements were also observed in DASH (46.8±9.1 to 40.8±9.3) and IPAQ (1136.3±612.8 to 1287±664.1).
Conclusion
The KMR exercise program effectively improved the physical function, alleviated edema, reduced upper extremity disability, and enhanced the QOL in breast cancer survivors. Coupled with significant group-by-time interactions for various outcomes, the results emphasize the potential benefits of incorporating the KMR exercise program to improve the QOL in breast cancer survivors.

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Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Received March 23, 2024 Accepted August 18, 2024 Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296 [Accepted]

Abstract PDF Supplementary Material: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform – FiRST Cancer Panel (FCP) – over seven years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. 97.6% of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53(56.2%), PIK3CA(31.2%), GATA3(13.8%), BRCA2(10.2%), and amplifications of CCND1(10.8%), FGF19(10.0%), and ERBB2(9.5%). NGS analysis of ERBB2 amplification correlated well with HER2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. 10.3% of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Trends in Cancer-Screening Rates in Korea: Findings from the National Cancer Screening Survey, 2004-2023: EunKyo Kang, Kui Son Choi, Jae Kwan Jun, Yeol Kim, Hyeon Ji Lee, Chang Kyun Choi, Tae Hee Kim, Sun Hwa Lee, Mina Suh; Received March 31, 2024 Accepted August 1, 2024 Published online August 2, 2024; DOI: https://doi.org/10.4143/crt.2024.325 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
This study aimed to report the overall national trends in the rates of cancer screening based on recommendations and provide insights into the changing trends of these rates across different demographics.
Materials and Methods
This study used data from the Korean National Cancer Screening Survey (KNCSS), which surveys nationwide cancer-screening rates and includes 4,500 individuals meeting the Korean National Cancer Screening Program (NCSP) protocol age criteria. Cancer-screening rates were assessed using structured questionnaires; yearly trends were analyzed for both lifetime cancer-screening rates and rates of screening based on recommendations, and subgroup analyses were performed based on age and sex.
Results
The rates of cancer screening based on recommendations showed significant increments: the stomach cancer-screening rate increased from 39.2% in 2004 to 77.5% in 2023 (3.50% per year), the liver cancer-screening rate increased from 20.0% to 48.8% (4.30% per year), and the colorectal cancer, increased from 19.9% to 70.7% (5.15% per year). The breast cancer-screening rate increased from 33.2% to 72.7% (2.88% per year), and the cervical cancer, increased from 58.3% to 70.2% (1.08% per year). Despite some differences, particularly in relation to sociodemographic factors, screening rates increased significantly for all cancer types.
Conclusion
Cancer-screening rates in Korea increased consistently from 2004 to 2023, demonstrating the effectiveness of the national cancer-screening program. However, the increments in breast, cervical and lung cancer-screening rates were relatively lower, indicating the need for additional efforts and strategies.

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Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14): Sang Min Lee, Bum-Sup Jang, Won Park, Yong Bae Kim, Jin Ho Song, Jin Hee Kim, Tae Hyun Kim, In Ah Kim, Jong Hoon Lee, Sung-Ja Ahn, Kyubo Kim, Ah Ram Chang, Jeanny Kwon, Hae Jin Park, Kyung Hwan Shin; Received February 23, 2024 Accepted July 11, 2024 Published online July 12, 2024; DOI: https://doi.org/10.4143/crt.2024.201 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data.
Materials and Methods
A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed.
Results
Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS.
Conclusion
BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

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A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of ¹⁸F-FES PET-CT and Metabolites with Treatment Response: Qing Shao, Ningning Zhang, Xianjun Pan, Wenqi Zhou, Yali Wang, Xiaoliang Chen, Jing Wu, Xiaohua Zeng; Received November 24, 2023 Accepted July 7, 2024 Published online July 9, 2024; DOI: https://doi.org/10.4143/crt.2023.1251 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (¹⁸F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received ¹⁸F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of ¹⁸F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. ¹⁸F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

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Molecular Classification of Breast Cancer Using Weakly Supervised Learning: Wooyoung Jang, Jonghyun Lee, Kyong Hwa Park, Aeree Kim, Sung Hak Lee, Sangjeong Ahn; Received February 5, 2024 Accepted June 23, 2024 Published online June 25, 2024; DOI: https://doi.org/10.4143/crt.2024.113 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
The molecular classification of breast cancer is crucial for effective treatment. The emergence of digital pathology has ushered in a new era in which weakly supervised learning leveraging whole-slide images has gained prominence in developing deep learning models because this approach alleviates the need for extensive manual annotation. Weakly supervised learning was employed to classify the molecular subtypes of breast cancer.
Materials and Methods
Our approach capitalizes on two whole-slide image datasets: one consisting of breast cancer cases from the Korea University Guro Hospital (KG) and the other originating from The Cancer Genomic Atlas dataset (TCGA). Furthermore, we visualized the inferred results using an attention-based heat map and reviewed the histomorphological features of the most attentive patches.
Results
The KG+TCGA-trained model achieved an area under the receiver operating characteristics value of 0.749. An inherent challenge lies in the imbalance among subtypes. Additionally, discrepancies between the two datasets resulted in different molecular subtype proportions. To mitigate this imbalance, we merged the two datasets, and the resulting model exhibited improved performance. The attentive patches correlated well with widely recognized histomorphologic features. The triple-negative subtype has a high incidence of high-grade nuclei, tumor necrosis, and intratumoral tumor-infiltrating lymphocytes. The luminal A subtype showed a high incidence of collagen fibers.
Conclusion
The artificial intelligence (AI) model based on weakly supervised learning showed promising performance. A review of the most attentive patches provided insights into the predictions of the AI model. AI models can become invaluable screening tools that reduce costs and workloads in practice.

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Endoxifen Concentration Is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients: Beomki Lee, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung-Joo Chae, Se Kyung Lee, Jai Min Ryu, Jeong Eon Lee, Soo-Youn Lee; Received December 5, 2023 Accepted June 16, 2024 Published online June 18, 2024; DOI: https://doi.org/10.4143/crt.2023.1285 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dose. However, the clinical significance of endoxifen for the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication.
Materials and Methods
The study included 478 breast cancer patients. Tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry. An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff.
Results
An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and the high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% confidence interval [CI], 77.0 to 89.9) and 88.3% (95% CI, 83.3 to 93.5) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor associated with prognosis.
Conclusion
Endoxifen could serve as a marker for appropriate tamoxifen treatment with a cutoff of 21.00 ng/mL. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying suboptimal endoxifen concentrations.

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Breast cancer

A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Kyunghee Park, Jong-Han Yu, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong; Cancer Res Treat. 2024;56(4):1113-1125. Published online May 10, 2024; DOI: https://doi.org/10.4143/crt.2024.100

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

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Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan’s National Database
Kyoka Kawabata, Hinano Nishikubo, Saki Kanei, Rika Aoyama, Yuki Tsukada, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Qiang Wang, Zhonglin Zhu, Canfeng Fan, Masakazu Yashiro
Genes.2024; 15(6): 792. CrossRef

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Dural Metastasis in Breast Cancer: MRI-Based Morphological Subtypes and Their Clinical Implications: Sung Jun Ahn, Bio Joo, Mina Park, Hun Ho Park, Sang Hyun Suh, Sung Gwe Ahn, Jihwan Yoo; Cancer Res Treat. 2024;56(4):1105-1112. Published online March 19, 2024; DOI: https://doi.org/10.4143/crt.2024.138

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the clinical factors associated with breast cancer (BRCA) dural metastases (DMs), their impact on prognosis compared to brain parenchymal metastases (BPMs) alone, and differences between DM subtypes, aiming to inform clinical decisions.
Materials and Methods
We retrospectively analyzed 119 patients with BRCA with brain metastasis, including 91 patients with BPM alone and 28 patients with DM. Univariate and multivariate analyses were performed to compare the clinical characteristics between the two groups and within subtypes of DM. Overall survival after DM (OSDM) and the interval from DM to leptomeningeal carcinomatosis (LMC) were compared using Kaplan-Meier analysis.
Results
DM was notably linked with extracranial metastasis, luminal-like BRCA subtype (p=0.033), and skull metastases (p < 0.001). Multiple logistic regression revealed a strong association of DM with extracranial and skull metastases, but not with subtype or hormone receptor status. Patients with DM did not show survival differences compared with patients with BPM alone. In the subgroup analysis, nodular-type DM correlated with human epidermal growth factor receptor 2 status (p=0.044), whereas diffuse-type DM was significantly associated with a higher prevalence of the luminal-like subtype (p=0.048) and the presence of skull metastasis (p=0.002). Patients with diffuse DM did not exhibit a significant difference in OSDM but had a notably shorter interval from DM to LMC compared to those with nodular DM (p=0.049).
Conclusion
While the impact of DM on the overall prognosis of patients with BRCA is minimal, our findings underscore distinct characteristics and prognostic outcomes within DM subgroups.

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Small-cell neuroendocrine carcinoma of the cervix with leptomeningeal spread: A rare coincidence report and literature review
Mohammed A. Azab, Oday Atallah, Nour El-Gohary, Ahmed Hazim, Hamed Abdelma’aboud Mostafa
Surgical Neurology International.2024; 15: 310. CrossRef
Left homonymous hemianopia as an atypical manifestation of isolated pachymeningeal metastasis secondary to breast cancer: Case report and review of the literature
Aziz Ahizoune, Moad Belouad, Houda Alloussi, Mohamed Allaoui, Mohamed Hamid, Ahmed Bourazza
Radiology Case Reports.2024; 19(11): 5459. CrossRef

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A Nationwide Study on HER2-Low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols: Min Chong Kim, Eun Yoon Cho, So Yeon Park, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Ho-chang Lee, Jin Ye Yoo, Hee Sung Kim, Bomi Kim, Wan Seop Kim, Nari Shin, Young Hee Maeng, Hun Soo Kim, Sun Young Kwon, Chungyeul Kim, Sun-Young Jun, Gui Young Kwon, Hye Jeong Choi, So Mang Lee, Ji Eun Choi, Ae Ri An, Hyun Joo Choi, EunKyung Kim, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; Cancer Res Treat. 2024;56(4):1096-1104. Published online March 6, 2024; DOI: https://doi.org/10.4143/crt.2024.092

Abstract PDF Supplementary Material PubReader ePub

Purpose
Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results.
Materials and Methods
The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected.
Results
Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients.
Conclusion
The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

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Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer
Min Chong Kim, Sun Young Kwon, Hye Ra Jung, Young Kyung Bae
Virchows Archiv.2024;[Epub] CrossRef
Breast Cancer: Extracellular Matrix and Microbiome Interactions
Lourdes Herrera-Quintana, Héctor Vázquez-Lorente, Julio Plaza-Diaz
International Journal of Molecular Sciences.2024; 25(13): 7226. CrossRef

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Implementation of BRCA Test among Young Breast Cancer Patients in South Korea: A Nationwide Cohort Study: Yung-Huyn Hwang, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Beom Seok Ko, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, Il Yong Chung; Cancer Res Treat. 2024;56(3):802-808. Published online February 19, 2024; DOI: https://doi.org/10.4143/crt.2023.1186

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea.
Materials and Methods
We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing.
Results
From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively.
Conclusion
The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.

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HER2-Low Breast Cancer: Now and in the Future: Sora Kang, Sung-Bae Kim; Cancer Res Treat. 2024;56(3):700-720. Published online January 30, 2024; DOI: https://doi.org/10.4143/crt.2023.1138

Abstract PDF PubReader ePub: Breast cancer is a heterogeneous disease, and its subtypes are characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) expression status. “HER2-low” tumors, which exhibit a low level of HER2 expression (immunohistochemistry 1+ or 2+ without gene amplification), were conventionally considered not amenable to anti-HER2 targeting agents based on the results of a phase III trial of trastuzumab. However, this perspective is being challenged by the emergence of novel anti-HER2 antibody-drug conjugates, such as trastuzumab-deruxtecan. These innovative therapies have demonstrated remarkable efficacy against HER2-low breast cancer, shedding new light on a previously overlooked category of breast cancer. Such promising results highlight the need for in-depth investigations of the biology and prognostic implications of HER2-low tumors. In this review, we comprehensively summarize the current evidence surrounding this topic and highlight areas that warrant further exploration and research in the future.

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Breast cancer

PD-L1 (SP142) Expression in Primary and Recurrent/Metastatic Triple-Negative Breast Cancers and Its Clinicopathological Significance: Eun Kyung Han, Ji Won Woo, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park; Cancer Res Treat. 2024;56(2):557-566. Published online December 12, 2023; DOI: https://doi.org/10.4143/crt.2023.1025

Abstract PDF PubReader ePub

Purpose
The programmed death-ligand 1 (PD-L1) SP142 assay identifies patients with triple-negative breast cancer (TNBC) who are most likely to respond to the anti–PD-L1 agent atezolizumab. We aimed to compare PD-L1 (SP142) expression between primary and recurrent/metastatic TNBCs and elucidate the clinicopathological features associated with its expression.
Materials and Methods
Primary and recurrent/metastatic TNBCs tested with PD-L1 (SP142) were collected, and clinicopathological information of these cases was obtained through a review of slides and medical records.
Results
PD-L1 (SP142) positivity was observed in 50.9% (144/283) of primary tumors and 37.8% (31/82) of recurrent/metastatic TNBCs with a significant difference. Recurrent or metastatic sites were associated with PD-L1 positivity, with high PD-L1 positivity in the lung, breast, and soft tissues, and low positivity in the bone, skin, liver, and brain. When comparing PD-L1 expression between primary and matched recurrent/metastatic TNBCs using 55 paired samples, 20 cases (36.4%) showed discordance; 10 cases revealed positive conversion, and another 10 cases revealed negative conversion during metastatic progression. In primary TNBCs, PD-L1 expression was associated with a higher histologic grade, lower T category, pushing border, and higher tumor-infiltrating lymphocyte infiltration. In survival analyses, PD-L1 positivity, especially high positivity, was found to be associated with favorable prognosis of patients.
Conclusion
PD-L1 (SP142) expression was lower in recurrent/metastatic TNBCs, and substantial cases showed discordance in its expression between primary and recurrent/metastatic sites, suggesting that multiple sites may need to be tested for PD-L1 (SP142) when considering atezolizumab therapy. PD-L1 (SP142)–positive TNBCs seems to be associated with favorable clinical outcomes.

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Solamargine inhibits gastric cancer progression via inactivation of STAT3/PD‑L1 signaling
Xiongxiang Liu, Lin Song, Wen Liu, Bin Liu, Lang Liu, Yao Su
Molecular Medicine Reports.2024;[Epub] CrossRef

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Genomic Characteristics and Its Therapeutic Implications in Breast Cancer Patients with Detectable Molecular Residual Disease: Shu Zhang, Yan Jiang, Lu Zhou, Jing Xu, Gang Zhang, Lu Shen, Yan Xu; Cancer Res Treat. 2024;56(2):538-548. Published online December 5, 2023; DOI: https://doi.org/10.4143/crt.2023.1059

Abstract PDF Supplementary Material PubReader ePub: Purpose
Molecular residual disease (MRD) is the main cause of postoperative recurrence of breast cancer. However, the baseline tumor genomic characteristics and therapeutic implications of breast cancer patients with detectable MRD after surgery are still unknown.
Materials and Methods
In this study, we enrolled 80 patients with breast cancer who underwent next-generation sequencing-based genetic testing of 1,021 cancer-related genes performed on baseline tumor and postoperative plasma, among which 18 patients had detectable MRD after surgery.
Results
Baseline clinical characteristics found that patients with higher clinical stages were more likely to have detectable MRD. Analysis of single nucleotide variations and small insertions/deletions in baseline tumors showed that somatic mutations in MAP3K1, ATM, FLT1, GNAS, POLD1, SPEN, and WWP2 were significantly enriched in patients with detectable MRD. Oncogenic signaling pathway analysis revealed that alteration of the Cell cycle pathway was more likely to occur in patients with detectable MRD (p=0.012). Mutational signature analysis showed that defective DNA mismatch repair and activation-induced cytidine deaminase (AID) mediated somatic hypermutation (SHM) were associated with detectable MRD. According to the OncoKB database, 77.8% (14/18) of patients with detectable MRD had U.S. Food and Drug Administration–approved mutational biomarkers and targeted therapy.
Conclusion
Our study reports genomic characteristics of breast cancer patients with detectable MRD. The cell cycle pathway, defective DNA mismatch repair, and AID-mediated SHM were found to be the possible causes of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.

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Implication of Pre- and Post-radiotherapy ctDNA Dynamics in Patients with Residual Triple-Negative Breast Cancer at Surgery after Neoadjuvant Chemotherapy: Findings from a Prospective Observational Study: Tae Hoon Lee, Haeyoung Kim, Yeon Jeong Kim, Woong-Yang Park, Won Park, Won Kyung Cho, Nalee Kim; Cancer Res Treat. 2024;56(2):531-537. Published online November 10, 2023; DOI: https://doi.org/10.4143/crt.2023.996

Abstract PDF PubReader ePub

Purpose
This study aims to determine the association between pre- and postoperative radiotherapy (PORT) circulating tumor DNA (ctDNA) dynamics and oncological outcomes in patients with residual triple-negative breast cancer who underwent surgery after neoadjuvant chemotherapy (NAC).
Materials and Methods
Between March 2019 and July 2020, 11 nonmetastatic patients with residual disease who underwent surgery after NAC were prospectively enrolled. In each patient, tumor specimens obtained during surgery and blood samples collected at three time points during PORT (T0: pre-PORT, T1: 3 weeks after PORT, T2: 1 month after PORT) were sequenced, targeting 38 cancer-related genes. Disease-free survival (DFS) was evaluated and the association between DFS and ctDNA dynamics was analyzed.
Results
At T0, ctDNA was detected in three (27.2%) patients. The ctDNA dynamics were as follows: two showed a decreasing ctDNA variant allele frequency (VAF) and reached zero VAF at T2, while one patient exhibited an increasing VAF during PORT and maintained an elevated VAF at T2. After a median follow-up of 48 months, two patients experienced distant metastasis without any locoregional failures. All failures occurred in patients with ctDNA positivity at T0 and a decreased VAF after PORT. The 4-year DFS rates according to the T0 ctDNA status were 67% (positive ctDNA) and 100% (negative ctDNA) (p=0.032).
Conclusion
More than a quarter of the patients with residual disease after post-NAC surgery exhibited pre-PORT ctDNA positivity, and ctDNA positivity was associated with poor DFS. For patients with pre-PORT ctDNA positivity, the administration of a more effective systemic treatment should be considered.

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Multiple drugs

Reactions Weekly.2024; 2033(1): 183. CrossRef

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Temporal Trend in Uptake of the National General Health Checkups and Cancer Screening Program among Korean Women with Breast Cancer: Thi Xuan Mai Tran, Soyeoun Kim, Chihwan Cha, Boyoung Park; Cancer Res Treat. 2024;56(2):522-530. Published online October 30, 2023; DOI: https://doi.org/10.4143/crt.2023.729

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study assessed the temporal trends of uptake of national general health and cancer screening among women with breast cancer in Korea between 2009 and 2016.
Materials and Methods
We retrospectively analyzed the claims data from the Korean National Health Insurance Service database. Participants included 101,403 breast cancer patients diagnosed between 2009 and 2016. Information on participation in national screening programs, including breast cancer screening, general health, and gastric, colorectal, and cervical cancers, up to 2020 was collected. Screening participation rates within the first 2 and 5 years postdiagnosis were calculated by diagnosis year and fitted with joinpoint regression models to assess temporal trends.
Results
Overall, the participation rate in breast cancer screening within 2 years postdiagnosis increased from 10.9% to 14.0% from 2009-2016, with an annual percentage change (APC) of 3.7% (p < 0.05). The participation rate in breast cancer screening was lower than that in general health checkup and screening for other cancers within 2 and 5 years postdiagnosis. A steady increase in screening trends was also observed for general health, gastric, colorectal, and cervical cancers, with APC of 5.3%, 5.7%, 6.9%, and 7.6% in the 2-year postdiagnosis rate, and APC of 3.6%, 3.7%, 3.7%, and 4.4% in 5-year postdiagnosis rate, respectively. The screening rate was highest among age groups 50-59 and 60-69 in 2009 and significant upward trends were observed in all age groups for general health checkup and gastric, colorectal, and cervical cancer screening.
Conclusion
Among female breast cancer survivors in Korea, the uptake rate of screenings for general health and various cancers, including breast, gastric, colorectal, and cervical cancers, has shown a gradual increase in recent years.

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Screening Adherence for Second Primary Malignancies in Breast Cancer Survivors: Behaviors, Facilitators, and Barriers to Enhance Quality Care
Fernanda Mesa-Chavez, Misael Salazar-Alejo, Cynthia Villarreal-Garza
Seminars in Oncology.2024;[Epub] CrossRef

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Pyrotinib Combined with Vinorelbine in Patients with Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Single-Arm, Prospective Study: Kuikui Jiang, Ruoxi Hong, Wen Xia, Qianyi Lu, Liang Li, Jianhao Huang, Yanxia Shi, Zhongyu Yuan, Qiufan Zheng, Xin An, Cong Xue, Jiajia Huang, Xiwen Bi, Meiting Chen, Jingmin Zhang, Fei Xu, Shusen Wang; Cancer Res Treat. 2024;56(2):513-521. Published online October 12, 2023; DOI: https://doi.org/10.4143/crt.2023.786

Abstract PDF PubReader ePub

Purpose
This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice.
Materials and Methods
This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m² intravenously or 60-80 mg/m² orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety.
Results
A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%).
Conclusion
Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

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Unraveling the future: Innovative design strategies and emerging challenges in HER2-targeted tyrosine kinase inhibitors for cancer therapy
Sixiang Zheng, Ruixian Chen, Lele Zhang, Lun Tan, Lintao Li, Fangyi Long, Ting Wang
European Journal of Medicinal Chemistry.2024; 276: 116702. CrossRef
Pyrotinib combined with metronomic etoposide in heavily pretreated HER2-positive metastatic breast cancer: a single-arm, phase II study
Jiaxuan Liu, Maiyue He, Mingxia Jiang, Shihan Zhou, Mengqi Zhang, Yiqun Li, Shanshan Chen, Ruigang Cai, Hongnan Mo, Bo Lan, Fei Ma, Binghe Xu, Qiao Li
BMC Cancer.2024;[Epub] CrossRef

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Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer: Eunice Yoojin Lee, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im; Cancer Res Treat. 2023;55(4):1065-1076. Published online October 5, 2023; DOI: https://doi.org/10.4143/crt.2023.846

Abstract PDF PubReader ePub

Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

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Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions
Rohan Kalyan Rej, Joyeeta Roy, Srinivasa Rao Allu
Cancers.2024; 16(3): 552. CrossRef

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Breast cancer

Short-term Impact of Hormone Replacement Therapy on Risk of Breast Cancer in BRCA Mutation Carriers: A Nationwide Study in South Korea: Hye Yeon Kim, Jisoo Park, Seok Joo Moon, Sohyeon Jeong, Jin Hwa Hong, Jae Kwan Lee, Geum Joon Cho, Hyun-Woong Cho; Cancer Res Treat. 2024;56(1):143-148. Published online August 16, 2023; DOI: https://doi.org/10.4143/crt.2023.653

Abstract PDF PubReader ePub

Purpose
BRCA1/2 mutations are well-known risk factors for breast and ovarian cancers in women. Risk-reducing salpingo-oophorectomy (RRSO) is the standard treatment for preventing ovarian cancer with BRCA mutations. Postmenopausal syndrome (symptoms after RRSO can be alleviated by hormone replacement therapy (HRT); however, the use of HRT in carriers of BRCA mutations has been controversial because of the concern that HRT increases the risk of breast cancer. This study aimed to evaluate the effects of HRT in BRCA mutation carriers who underwent RRSO.
Materials and Methods
A total of 151 carriers, who underwent RRSO between 2013 and 2020 after the diagnosis of BRCA1 or BRCA2 mutations were selected and followed up for a median of 3.03 years. Patients were divided into two groups: those who received HRT after RRSO (n=33) and those who did not (n=118). We compared the incidence of breast cancer over time between these two groups.
Results
There was no significant difference in the incidence of breast cancer between women who received HRT and those who did not (p=0.229). Multivariate logistic regression analysis, adjusted for age and parity revealed no significant difference in the risk of breast cancer between these two groups (hazard ratio, 0.312; 95% confidence interval, 0.039 to 2.480; p=0.278).
Conclusion
In this study, we found no relationship between post-RRSO HRT and breast cancer in the population with BRCA mutations. Therefore, healthcare providers may consider the alleviation of symptoms of postmenopausal syndrome through HRT in patients who underwent RRSO.

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A contemporary review of breast cancer risk factors and the role of artificial intelligence
Orietta Nicolis, Denisse De Los Angeles, Carla Taramasco
Frontiers in Oncology.2024;[Epub] CrossRef

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Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes: Xin Li, Zehao Li, Lin Li, Tong Liu, Cheng Qian, Yanlv Ren, Zhigao Li, Kejin Chen, Dongchen Ji, Ming Zhang, Jinsong Wang; Cancer Res Treat. 2024;56(1):134-142. Published online August 14, 2023; DOI: https://doi.org/10.4143/crt.2023.652

Abstract PDF PubReader ePub

Purpose
Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes.
Materials and Methods
CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group.
Results
A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003).
Conclusion
Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

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FDA-approved drugs containing dimethylamine pharmacophore: a review of the last 50 years
Sandeep Bindra, Kuntal Bose, Amrutha Chandran Thekkantavida, Della Grace Thomas Parambi, Tariq G. Alsahli, Manu Pant, Leena K. Pappachen, Hoon Kim, Bijo Mathew
RSC Advances.2024; 14(38): 27657. CrossRef

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Next-Generation Sequencing in Breast Cancer Patients: Real-World Data for Precision Medicine: Hyunwoo Lee, Yoon Ah Cho, Deok Geun Kim, Eun Yoon Cho; Cancer Res Treat. 2024;56(1):149-161. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.800

Abstract PDF Supplementary Material PubReader ePub

Purpose
Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer.
Materials and Methods
We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500.
Results
The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation.
Conclusion
NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies.

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Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+/HER2- metastatic breast cancer
Elena Guerini-Rocco, Konstantinos Venetis, Giulia Cursano, Eltjona Mane, Chiara Frascarelli, Francesco Pepe, Mariachiara Negrelli, Edoardo Olmeda, Davide Vacirca, Alberto Ranghiero, Dario Trapani, Carmen Criscitiello, Giuseppe Curigliano, Christian Rolfo,
Critical Reviews in Oncology/Hematology.2024; 201: 104427. CrossRef
An ultra-sensitive and rapid immunosensor for the onsite detection of circulating tumor DNA in breast cancer
Yi Bi, Xiao Lv, Ke Wang, Jinyu Wu, Xiang Shi, Xiaodong Zheng, Xiaogang Lin
Frontiers in Bioengineering and Biotechnology.2024;[Epub] CrossRef
NGS mutational status on first diagnostic tissue, liquid biopsy and mastectomy in G2–G3 breast cancer
Carmen Maria Ardeleanu, Maria Victoria Olinca , Cristian Gabriel Viişoreanu , Horaţiu Alin Mureşan , Adriana Tecuceanu-Vulpe , Georgiana Manole , Iulia Elena Gune , Bianca Gălăţeanu , Andreea-Corina Ilie-Petrov
Romanian Journal of Morphology and Embryology.2024; 65(2): 195. CrossRef

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Changes in Invasive Breast Carcinomas after Neoadjuvant Chemotherapy Can Influence Adjuvant Therapeutic Decisions: Bárbara Jaime dos Santos, Débora Balabram, Virginia Mara Reis Gomes, Carolina Costa Café de Castro, Paulo Henrique Costa Diniz, Marcelo Araújo Buzelin, Cristiana Buzelin Nunes; Cancer Res Treat. 2024;56(1):178-190. Published online August 1, 2023; DOI: https://doi.org/10.4143/crt.2023.386

Abstract PDF PubReader ePub: Purpose
Neoadjuvant chemotherapy (NACT) can change invasive breast carcinomas (IBC) and influence the patients’ overall survival time (OS). We aimed to identify IBC changes after NACT and their association with OS.
Materials and Methods
IBC data in pre- and post-NACT samples of 86 patients were evaluated and associated with OS.
Results
Post-NACT tumors changed nuclear pleomorphism score (p=0.025); mitotic count (p=0.002); % of tumor-infiltrating inflammatory cells (p=0.016); presence of in situ carcinoma (p=0.001) and lymphovascular invasion (LVI; p=0.002); expression of estrogen (p=0.003), progesterone receptors (PR; p=0.019), and Ki67 (p=0.003). Immunohistochemical (IHC) profile changed in 26 tumors (30.2%, p=0.050). Higher risk of death was significatively associated with initial tumor histological grade III (hazard ratio [HR], 2.94), high nuclear pleomorphism (HR, 2.53), high Ki67 index (HR, 2.47), post-NACT presence of LVI (HR, 1.90), luminal B–like profile (HR, 2.58), pre- (HR, 2.26) and post-NACT intermediate mitotic count (HR, 2.12), pre- (HR, 4.45) and post-NACT triple-negative IHC profile (HR, 4.52). On the other hand, lower risk of death was significative associated with pre- (HR, 0.35) and post-NACT (HR, 0.39) estrogen receptor–positive, and pre- (HR, 0.37) and post-NACT (HR, 0.57) PR-positive. Changes in IHC profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III tumors and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS.
Conclusion
NACT can change tumor characteristics and biomarkers and impact on OS; therefore, they should be reassessed on residual samples to improve therapeutic decisions.

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Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy: Dongjin Kim, Yeuni Yu, Ki Sun Jung, Yun Hak Kim, Jae-Joon Kim; Cancer Res Treat. 2024;56(1):162-177. Published online July 24, 2023; DOI: https://doi.org/10.4143/crt.2023.330

Abstract PDF Supplementary Material PubReader ePub

Purpose
Triple-negative breast cancer (TNBC) is a breast cancer subtype that has poor prognosis and exhibits a unique tumor microenvironment. Analysis of the tumor microbiome has indicated a relationship between the tumor microenvironment and treatment response. Therefore, we attempted to reveal the role of the tumor microbiome in patients with TNBC receiving neoadjuvant chemotherapy.
Materials and Methods
We collected TNBC patient RNA-sequencing samples from the Gene Expression Omnibus and extracted microbiome count data. Differential and relative abundance were estimated with linear discriminant analysis effect size. We calculated the immune cell fraction with CIBERSORTx and conducted survival analysis using the Cancer Genome Atlas patient data. Correlations between the microbiome and immune cell compositions were analyzed and a prediction model was constructed to estimate drug response.
Results
Among the pathological complete response group (pCR), the beta diversity varied considerably; consequently, 20 genera and 24 species were observed to express a significant differential and relative abundance. Pandoraea pulmonicola and Brucella melitensis were found to be important features in determining drug response. In correlation analysis, Geosporobacter ferrireducens, Streptococcus sanguinis, and resting natural killer cells were the most correlated factors in the pCR, whereas Nitrosospira briensis, Plantactinospora sp. BC1, and regulatory T cells were key features in the residual disease group.
Conclusion
Our study demonstrated that the microbiome analysis of tumor tissue can predict chemotherapy response of patients with TNBC. Further, the immunological tumor microenvironment may be impacted by the tumor microbiome, thereby affecting the corresponding survival and treatment response.

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Shotgun Metagenomics Reveals Minor Micro“bee”omes Diversity Defining Differences between Larvae and Pupae Brood Combs
Daniil Smutin, Amir Taldaev, Egor Lebedev, Leonid Adonin
International Journal of Molecular Sciences.2024; 25(2): 741. CrossRef

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General

Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients: Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong; Cancer Res Treat. 2023;55(4):1077-1086. Published online June 12, 2023; DOI: https://doi.org/10.4143/crt.2022.1630

Abstract PDF Supplementary Material PubReader ePub

Purpose
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

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PRMT1 promotes pancreatic cancer development and resistance to chemotherapy
Bomin Ku, David Eisenbarth, Seonguk Baek, Tae-Keun Jeong, Ju-Gyeong Kang, Daehee Hwang, Myung-Giun Noh, Chan Choi, Sungwoo Choi, Taejun Seol, Hail Kim, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong, Dae-Sik Lim
Cell Reports Medicine.2024; 5(3): 101461. CrossRef
Establishment and Advancement of Pancreatic Organoids
Dong Hyeon Lee
Keimyung Medical Journal.2024; 43(1): 3. CrossRef
Organoid as a promising tool for primary liver cancer research: a comprehensive review
Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni
Cell & Bioscience.2024;[Epub] CrossRef
The use of organoids in creating immune microenvironments and treating gynecological tumors
Ling-Feng Zhou, Hui-Yan Liao, Yang Han, Yang Zhao
Journal of Translational Medicine.2024;[Epub] CrossRef
Organoid: Bridging the gap between basic research and clinical practice
Guihu Weng, Jinxin Tao, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Taiping Zhang
Cancer Letters.2023; 572: 216353. CrossRef

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Breast cancer

Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy: Youzhao Ma, Mingda Zhu, Jingyang Zhang, Minhao Lv, Xiuchun Chen, Zhenzhen Liu; Cancer Res Treat. 2023;55(4):1210-1221. Published online April 4, 2023; DOI: https://doi.org/10.4143/crt.2022.1633

Abstract PDF PubReader ePub

Purpose
Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT).
Materials and Methods
The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined.
Results
Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016).
Conclusion
Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Citations

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The Modified Neo-Bioscore System for Staging Breast Cancer Treated with Neoadjuvant Therapy Based on Prognostic Significance of HER2-Low Expression
Yingying Zhao, Xinru Chen, Yaohui Wang, Xueqing Zhang, Jingsong Lu, Wenjin Yin
Journal of Clinical Medicine.2024; 13(7): 1850. CrossRef
Preoperative Differentiation of HER2‐Zero and HER2‐Low from HER2‐Positive Invasive Ductal Breast Cancers Using BI‐RADS MRI Features and Machine Learning Modeling
Jiejie Zhou, Yang Zhang, Haiwei Miao, Ga Young Yoon, Jinhao Wang, Yezhi Lin, Hailing Wang, Yan‐Lin Liu, Jeon‐Hor Chen, Zhifang Pan, Min‐Ying Su, Meihao Wang
Journal of Magnetic Resonance Imaging.2024;[Epub] CrossRef
Comparison of the Pathological Complete Response Rate and Survival Between HER2-Low and HER2-Zero Breast Cancer in Neoadjuvant Chemotherapy Setting: A Systematic Review and Meta-Analysis
Mei Liu, Qin Xiang, Fengsheng Dai, Yixiao Yuan, Zhongjun Wu, Tingxiu Xiang
Clinical Breast Cancer.2024; 24(7): 575. CrossRef
Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China
Shaorong Zhao, Yuyun Wang, Angxiao Zhou, Xu Liu, Yi Zhang, Jin Zhang
PeerJ.2024; 12: e17492. CrossRef
Alteration of HER2 Status During Breast Cancer Progression: A Clinicopathological Analysis Focusing on HER2-Low Status
Kyungah Bai, Ji Won Woo, Hyun Jung Kwon, Yul Ri Chung, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park
Laboratory Investigation.2024; 104(8): 102092. CrossRef
HER2-Low Breast Cancer: Now and in the Future
Sora Kang, Sung-Bae Kim
Cancer Research and Treatment.2024; 56(3): 700. CrossRef
Stable or at least once HER2-low status during neoadjuvant chemotherapy confers survival benefit in patients with breast cancer
Yingying Zhao, Xinru Chen, Yaohui Wang, Xueqing Zhang, Yumei Ye, Shuguang Xu, Liheng Zhou, Yanping Lin, Jingsong Lu, Wenjin Yin
Annals of Medicine.2024;[Epub] CrossRef
The prognostic impact of Her2 status in early triple negative breast cancer: a Turkish Oncology Group (TOG) study
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Prognostic implications of HER2 changes after neoadjuvant chemotherapy in patients with HER2-zero and HER2-low breast cancer
Sora Kang, So Heun Lee, Hee Jin Lee, Hyehyun Jeong, Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Gyungyub Gong, Hak Hee Kim, Saebyeol Lee, Jongwon Lee, Sung-Bae Kim
European Journal of Cancer.2023; : 112956. CrossRef

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Health-Seeking Behavior Returning to Normalcy Overcoming COVID-19 Threat in Breast Cancer: Eun-Gyeong Lee, Yireh Han, Dong-Eun Lee, Hyeong-Gon Moon, Hyoung Won Koh, Eun-Kyu Kim, So-Youn Jung; Cancer Res Treat. 2023;55(4):1222-1230. Published online April 3, 2023; DOI: https://doi.org/10.4143/crt.2023.364

Abstract PDF Supplementary Material PubReader ePub: Purpose
The coronavirus disease 2019 (COVID-19) outbreak has significantly impacted the diagnosis and treatment of breast cancer. Our study investigated the change in diagnosis and treatment of breast cancer with the progress of COVID-19 pandemic.
Materials and Methods
The study group comprised 6,514 recently diagnosed breast cancer patients between January 1, 2019, and February 28, 2021. The patients were divided into two groups: pre–COVID-19 period (3,182; January 2019 to December 2019) and COVID-19 pandemic period (3,332; January 2020 to February 2021). Clinicopathological information related to the first treatment after breast cancer diagnosis was retrospectively collected and analyzed in the two groups.
Results
Among the 6,514 breast cancer patients, 3,182 were in the pre–COVID-19 period and 3,332 were in the COVID-19 pandemic period. According to our evaluation, the least breast cancer diagnosis (21.8%) was seen in the first quarter of 2020. The diagnosis increased gradually except for the fourth quarter in 2020. While early-stage breast cancer was diagnosed 1,601 (48.1%) during the COVID-19 pandemic (p=0.001), the number of surgical treatments increased 4.6% (p < 0.001), and the treatment time was slightly shorter 2 days (p=0.001). The breast cancer subtype distribution was not statistically different between the pre–COVID-19 and COVID-19 period groups.
Conclusion
In the early stages of the pandemic, the number of breast cancer cases temporarily decreased; however, they stabilized soon, and no significant differences could be identified in the diagnosis and treatment when compared to the period before the pandemic.

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Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA: Jung-Ki Yoon, Jongseong Ahn, Sheehyun Kim, Hwang-Phil Kim, Jun-kyu Kang, Duhee Bang, Yoojoo Lim, Tae-You Kim; Cancer Res Treat. 2023;55(3):1048-1052. Published online January 31, 2023; DOI: https://doi.org/10.4143/crt.2022.1529

Abstract PDF Supplementary Material PubReader ePub

Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cell-free DNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.

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Circulating tumor DNA validity and potential uses in metastatic breast cancer
Ottavia Amato, Nefeli Giannopoulou, Michail Ignatiadis
npj Breast Cancer.2024;[Epub] CrossRef
DNA damage targeted therapy for advanced breast cancer
Vanessa Patel, Sandra Casimiro, Catarina Abreu, Tiago Barroso, Rita Teixeira de Sousa, Sofia Torres, Leonor Abreu Ribeiro, Gonçalo Nogueira-Costa, Helena Luna Pais, Conceição Pinto, Leila Costa, Luís Costa
Exploration of Targeted Anti-tumor Therapy.2024; 5(3): 678. CrossRef
Practical Utility of Liquid Biopsies for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer
Seung-Hwan Jeong, Dongsoo Kyung, Hyeong Dong Yuk, Chang Wook Jeong, Wookjae Lee, Jung-Ki Yoon, Hwang-Phill Kim, Duhee Bang, Tae-You Kim, Yoojoo Lim, Cheol Kwak
Cancers.2023; 15(10): 2847. CrossRef

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Breast cancer

Eflapegrastim versus Pegfilgrastim for Chemotherapy-Induced Neutropenia in Korean and Asian Patients with Early Breast Cancer: Results from the Two Phase III ADVANCE and RECOVER Studies: Yong Wha Moon, Seung Ki Kim, Keun Seok Lee, Moon Hee Lee, Yeon Hee Park, Kyong Hwa Park, Gun Min Kim, Seungtaek Lim, Seung Ah Lee, Jae Duk Choi, Eunhye Baek, Hyesun Han, Seungjae Baek, Seock-Ah Im; Cancer Res Treat. 2023;55(3):766-777. Published online January 19, 2023; DOI: https://doi.org/10.4143/crt.2022.987

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials.
Materials and Methods
Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations.
Results
Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations.
Conclusion
This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

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Comparison of Prophylactic Efficacy of Eflapegrastim and Pegteograstim for Chemotherapy-induced Neutropenia in Pancreatic Cancer Patients Receiving FOLFIRINOX/mFOLFIRINOX
Eui Seon Lee, Min Jung Geum, Jong Hee Ko, Jae Song Kim, Eun Sun Son, Yun Mi Yu
Journal of Korean Society of Health-System Pharmacists.2024; 41(3): 253. CrossRef

4,493 View
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