bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO2-01-05: Neoadjuvant pyrotinib plus trastuzumab, and chemoterapy in patients with HER2-positive early breast cancer: a real-world study
Authors: Zhou Jun , Wang Rui
Published: May 2024

Background Pyrotinib is a new oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor that targets human epidermal growth factor receptor 1 (HER1), HER2, and HER4. Previous studies have confirmed it combined with capecitabine is safe and well-tolerated in advanced breast cancer. And also PHEDRA trial had demonstrated the efficacy and safety of pyrotinib combined with trastuzumab and docetaxel neoadjuvant therapy early HER2-positive breast cancer. However, the efficacy of pyrotinib plus trastuzumab-based in real-world neoadjuvant therapy for early breast cancer is unknown. Purpose The present study aimed to explore the efficacy of pyrotinib-based in neoadjuvant therapy for early breast cancer in real-world. Method This is investigator-initiated phase 2 real-world study recruited eligible patients, aged 18–70 years with invasive carcinoma, cT2-3N0-3M0 stage, HER2-positive breast cancer. The patients received 400 mg pyrotinib orally once per day for 21 days and trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) plus different standard chemotherapy, including six 21-day cycles of docetaxel (75 mg/m2) plus carboplatin (6 mg/mL/min), or four cycles of epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) and four cycles paclitaxel (80 mg/m2). The primary endpoint was to calculate the number of patients who achieved a pathological complete response (pCR, ypT0/is, ypN0). (ChiCTR2100052892). Result The results of the 23 patients were reported, The pCR of 12 (52.2%) patients, who reached the threshold for the design, was noted. The study is ongoing. The most frequent grade 3 to 4 adverse events were diarrhea (35.6%), which all the patients received primary prevention of diarrhea, leukopenia (44.8%), and anaemia (23.7%). However, no treatment-related deaths were recorded. Conclusion Previous studies have shown the efficacy and safety of pyrotinib plus trastuzumab and docetaxel in neoadjuvant therapy of HER2-positive early breast cancer. The current trial suggests that pyrotinib plus trastuzumab-based standard chemotherapy in real-world has promising efficacy and manageable toxicity in patients with HER2-positive early breast cancer in a neoadjuvant setting, the trial is ongoing, we will enroll more patients.

Citation Format: Jun Zhou, Rui Wang. Neoadjuvant pyrotinib plus trastuzumab, and chemoterapy in patients with HER2-positive early breast cancer: a real-world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-05.
Abstract PO2-02-01: Online Virtual Patient Simulation CME Improves Clinical Decision-Making In The Management Of Patients With HR+/HER2- Early Breast Cancer
Authors: Dorkhom Nabil , Patel Urvi , Baumhover Stephanie , Cohen Jacob
Published: May 2024

Background:

The goal of this study is to assess whether an online, virtual patient simulation (VPS) continuing medical educational (CME) activity, improved the performance of oncologists in ordering appropriate diagnostic tests and managing and counselling patients with HR+/HER2- early breast cancer (EBC) at high risk of recurrence. Methods:

Two VPS educational activities were developed, the first VPS consisted of one patient case, focused on diagnosing patients with high risk of recurrence, while the other VPS consisted of 2 patient cases focused on the management and counselling of patients with HR+/HER2- EBC with high risk of recurrence. Physicians could make clinical decisions using complete open-field entries, based on the 3 performance based learning objectives. After each decision, learners received clinical guidance (CG) based on current evidence and expert recommendations. Pre- and post-CG clinical decisions were compared using a a McNemar's test to determine P values (P < .05 is significant). Rationales for clinical decisions were collected in real time. Data were collected between November 2021 and August 2022 and are reported here as % point change per performance learning objective, P value.

Results:

A total of 922 oncologists were included in the analysis. There was a significant improvement across the 3 performance learning objectives analysed.

Please see table below for the results. Conclusions:

This analysis demonstrated the educational impact of an immersive, online VPS education which allowed physicians to improve evidence-based clinical decisions regarding diagnosing patients with HR+/HER2- early breast cancer at high risk of recurrence and managing and counselling them regarding their treatment.

Results

Citation Format: Nabil Dorkhom, Urvi Patel, Stephanie Baumhover, Jacob Cohen. Online Virtual Patient Simulation CME Improves Clinical Decision-Making In The Management Of Patients With HR+/HER2- Early Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-01.
Abstract PO2-05-10: 'I am Still Alive': An Interpretative Phenomenological Analysis of Older Women Living with Metastatic Breast Cancer
Authors: Chidebe Runcie C.W. , Banwo-Fatai Khadijat , Agha Agha A. , Nwakanma-Akanno Onyedikachi C. , Narine Donnette , Yamashita Takashi , Platas Alejandra , Kinney Jennifer , Cummins Phyllis , Cardoso Fatima
Published: May 2024

Background: Metastatic breast cancer (mBC) is cancer that has spread from the primary organ (breast) to other distant organs such as bone, spine, lungs, brain, and liver. It is a treatable but incurable cancer. While the burden of mBC is devastating to all patients, older mBC patients have poorer prognoses, poor access to care and experience social isolation. This current study is aimed to explore the experiences of older women living with mBC and the impact of belonging to a peer support group (PSG) in Nigeria.

Method: Using interpretative phenomenological analysis (IPA), eight women living with mBC aged 50 and above participated in the semi-structured interview.

Results: Our findings showed that participants encountered psychological, physiological, and social challenges that are interrelated across four central themes: “Tormented by Pain,” “I am the One that is Going to Die,” “I am Not alone,” and “Winning the ‘war’ against mBC.” While the experiences of older women living with mBC were dominated by different levels of pain, death anxiety, stigma, and financial burden; belonging to a PSG brought participants hope, information, self-worth, and courage.

Conclusion: This study has shown PSG should be an important component of cancer control. Hence, healthcare leaders should support and fund the establishment of PSG across Nigeria. Whether mBC is curable or not, the last days of older women living with mBC should be filled with dignity, peer support, and the absence of pain.

Citation Format: Runcie C.W. Chidebe, Khadijat Banwo-Fatai, Agha A. Agha, Onyedikachi C. Nwakanma-Akanno, Donnette Narine, Takashi Yamashita, Alejandra Platas, Jennifer Kinney, Phyllis Cummins, Fatima Cardoso. 'I am Still Alive': An Interpretative Phenomenological Analysis of Older Women Living with Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-10.
Abstract PO2-06-09: A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC)
Authors: Zhang Liang , Sun Tao
Published: May 2024

Background: PD-1/PD-L1 inhibitor plus chemotherapy have shown tolerability and significant clinical benefits in pts with advanced TNBC. Antiangiogenic agent could remodel tumor blood vessels and increase the response to immune-checkpoint inhibitors (ICIs). AK105, an anti-PD-1 antibody, can effectively prevents PD-1 from binding to PD-L1 and PD-L2, and avoid immune evasion of tumor cells. Anlotinib is a novel antiangiogenic, multi-target tyrosine kinase inhibitor which inhibits VEGFR, FGFR, PDGFR, c-KIT, c-RET and MET. This investigator initiated trial (IIT) (NCT05244993) aims to investigate the efficacy and safety of AK105, anlotinib combined with nab-P as a first-line therapy in pts with advanced TNBC. Methods: In this multicenter, prospective, single arm, phase 2 study, eligible pts were female aged 18-75 years, with ECOG PS 0-1, who had locally advanced or recurrent/metastatic triple-negative (estrogen receptor-, progesterone receptor- and HER2-) breast cancer. Eligible pts were treated with intravenous AK105 (200 mg on day 1), oral anlotinib (12 mg once daily on days 1-14) and intravenous nab-P (125 mg/m2 on days 1 and 8) . The triplet combination regimen repeated every 21 days until disease progression, death or intolerable toxicity. The primary endpoint is overall response rate (ORR), and the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS)and safety. Results: From July 2022 to July 2023, 19 patients were enrolled in this study. Median follow-up was 6.18 months (95% CI 1.29-11.06). Of all the patients whose efficacy could be evaluated (16/19), no patient achieved complete response (CR); 9(56.25%), 6(37.5%) and 1(6.25%) patients got partial response (PR), stable disease (SD) and progression disease (PD), respectively. ORR was 56.25 % (95% CI 30.55-79.25) and DCR was 93.75% (95% CI 67.71-99.67). mPFS and OS have not reached. The most common adverse events (AEs) were grade 1 or 2. The grade 3 AEs were neutropenia (15.79%), Leukopenia (10.52%), elevated ALT (5.26%), elevated AST (5.26%) and hypercholesteremia (5.26%). There were one case of grade 4 neutropenia and one case of grade 4 hypertriglyceridemia. No treatment-related death was observed. Conclusion: The combination of AK105, anlotinib and nab-P showed better treatment response and tolerable toxicity in the treatment of first-line patients with TNBC. Further studies enrolling more patients are still needed.

Citation Format: Liang Zhang, Tao Sun. A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-09.
Abstract PO2-23-10: Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early Breast Cancer
Authors: Redfern Andrew , Agarwal Veenoo , Darcey Ellie , Spalding Lisa , Martin Hilary , Stone Jennifer
Published: May 2024

Background - An inverse association has been described in a number of studies between mammographic breast density (MBD) and pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early breast cancer (BC), implicating high MBD in chemotherapy resistance. However, this effect has not been seen in all there is a paucity of data exploring whether this relationship extends the relationship beyond pCR to overall survival. This study aims to validate the relationship between MBD and pCR in patients undergoing NAC for early BC as well as to assess the relation of MBD with clinical complete response (cCR), relapse-free (RFS) and BC-specific survival (BCSS). Further, this study examines these associations stratified by body mass index (BMI).

Methods - MBD was measured in contralateral mammograms in 127 women before NAC, using Cumulus software. As the study spanned the transition period from film to digital mammography, film mammograms were digitised using a high-powered scanner and processed full-field digital mammograms were extracted from the imaging storage facility. Basic patient, tumour and treatment demographics were collated including BMI. Percent dense area (PDA) was correlated with patient and tumour characteristics, short-term (pCR/cCR incidences), and long-term chemotherapy outcomes (RFS and BCSS).

Results - Overall rates of cCR and pCR of 49% and 21% were observed across the whole cohort. Mean PDA was higher in those not undergoing cCR (p=0.041) and relapsing patients (p=0.041) but did not significantly vary by pCR or BC-deaths. As a dichotomous variable, high PDA relative to low PDA corresponded to lower cCR (40 v 58%, p=0.027), but no significant difference was seen for pCR (17.5 v 25.0%, p=0.15), BC relapse (38 v 30%, p=0.15) or BC-death (32 v 25%, p=0.20). High PDA (relative to low PDA) in patients with obesity (BMI >30kg/m2) was associated with lower pCR (0% v 28.1%, p=0.036) and numerically higher relapse rates (56% v 28%, p=0.063) and breast cancer deaths (56 v 28%, p=0.071. No such relationship was observed in patients with a BMI< 30kg/m2.

Conclusion - Higher MBD associated with lower cCR and higher relapse but not with pCR or BC death. The inferior outcomes with high MBD were confined to patients with obesity in our study. Further analysis of the relationship between MBD and outcomes, including by BMI, is warranted.

Citation Format: Andrew Redfern, Veenoo Agarwal, Ellie Darcey, Lisa Spalding, Hilary Martin, Jennifer Stone. Obesity May Modulate the Relationship Between High Mammographic Breast Density and Neoadjuvant Chemoresistance in Early Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-10.
Abstract PO2-28-01: Deleting caveolin-1 in epithelial cells increases doxorubicin sensitivity in advance stage of breast cancer
Authors: Pandit Abhishek , Singh Dhirendra , Pathak Rashmi , Thota Shilpa , Francis Joseph
Published: May 2024

Caveolin-1 (Cav-1) is a lipid raft protein with a dual role, serving as a tumor suppressor and a promoter. Studies have unveiled Cav-1’s significance in breast cancer progression, impacting various aspects, including cell proliferation, apoptosis, autophagy, invasion, migration, and metastasis. Previously, our research demonstrated that the knockout (KO) of Cav-1 from epithelial cells reduced lung metastasis originating from primary tumors. In this study, we sought to investigate whether Cav-1 KO in epithelial cells increases sensitivity to doxorubicin (Dox) using both in vitro and in vivo studies. In our in vitro study, we observed reduced cell numbers in doxorubicin-treated Cav-1 KO cells compared to Dox-treated 4T1 cells (wild type). Flow cytometry-based cell cycle assay showed a significant increase in G2M phase arrest in Dox-treated Cav-1 KO cells compared with wild-type, confirming reduced cell growth and proliferation. To validate the increased sensitivity to Dox in vivo, we used a syngeneic tumor model using Cav-1 KO and 4T1 wild-type cells injected into the mammary fat of female Balb/c mice intraperitoneally. Subsequently, after one week of tumor cell injection, both groups received Dox at a dose of 8 mg/kg body weight/week for 3 weeks (a cumulative dose of 24 mg/kg body weight). Primary tumor sizes exhibited a significant reduction in Dox-treated mice, and this was further reduced in Cav-1 KO mice compared to the wild type. To quantify lung metastasis, we explanted the mice’s lungs and plated dissociated single cells in complete RPMI media supplemented with 6-thioguanine (6-GT). The number of 6-TG-resistant 4T1 metastatic cells was significantly lower in the lungs' suspension of Cav-1 KO mice treated with Dox compared to wild-type Dox-treated mice. Our findings confirm that knockout of Cav-1 increased the sensitivity of Dox treatment and inhibited breast cancer lung metastasis in Balb/c mice. Our ongoing analysis of the molecular pathways seeks to elucidate the underlying mechanism.

Citation Format: Abhishek Pandit, Dhirendra Singh, Rashmi Pathak, Shilpa Thota, Joseph Francis. Deleting caveolin-1 in epithelial cells increases doxorubicin sensitivity in advance stage of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-01.
Abstract PO3-01-08: Interaction of Prior Chemotherapy and Addition of Ovarian Function Suppression on Menopausal Symptoms in Tamoxifen-Treated Breast Cancer Patient: A prospective, Observational study
Authors: Lee Youngwon , Lee Jong Won , Lee Sae Byul , Son Byung Ho , Kim Hee Jeong , Ko Beom Seok , Kim Jisun , Chung Il-Yong , Yoo Tae-Kyung
Published: May 2024

Background: Adjuvant endocrine therapy (AET) is commonly used for hormone receptor-positive breast cancer patients. Combining ovarian function suppression (OFS) with tamoxifen improves survival outcomes, but is associated with menopausal symptom-related issues and treatment discontinuation. This study aimed to compare menopausal symptoms between tamoxifen alone and tamoxifen plus OFS over 12 months and identify related factors. Methods: This prospective study included 209 premenopausal breast cancer patients on tamoxifen. Menopausal symptoms were assessed using the Menopausal Rating Scale (MRS) at baseline, 3, 6, and 12 months. Statistical analysis involved linear regression and generalized estimating equations. Results: Of the participants, 27.8% received tamoxifen plus OFS and were younger and more likely to be unmarried. The tamoxifen plus OFS group had lower baseline MRS scores, but higher scores at 6 and 12 months compared to tamoxifen alone. MRS scores increased significantly in both groups, plateauing at 6 months with tamoxifen alone and at 12 months with tamoxifen plus OFS. Factors associated with higher MRS scores at 6 months were baseline MRS scores and addition of OFS. Impact of OFS on MRS scores varied with prior chemotherapy status, being significant in patients without prior chemotherapy. Conclusion: Adding OFS to tamoxifen in premenopausal breast cancer patients was associated with a higher burden of menopausal symptoms compared to tamoxifen alone, particularly in patients who have not undergone prior chemotherapy. Therefore, careful consideration and decision-making regarding this issue are crucial in terms of both treatment outcomes and quality of life.

Table 1. Baseline characteristics, Overall and According to adjuvant endocrine therapy, tamoxifen alone versus tamoxifen plus ovarian function suppression (OFS)

Table 2. Multivariable linear regression about MRS scores from the baseline to 6 months, and with interaction between addition of OFS and prior chemotherapy effect

Table 3. Interaction effect of additional OFS depending on prior chemotherapy; (a) without prior chemotherapy, (b) with prior chemotherapy

Citation Format: Youngwon Lee, Jong Won Lee, Sae Byul Lee, Byung Ho Son, Hee Jeong Kim, Beom Seok Ko, Jisun Kim, Il-Yong Chung, Tae-Kyung Yoo. Interaction of Prior Chemotherapy and Addition of Ovarian Function Suppression on Menopausal Symptoms in Tamoxifen-Treated Breast Cancer Patient: A prospective, Observational study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-08.
Abstract PO3-07-12: Effect of neoadjuvant chemotherapy on peritumoral edema in early stage breast cancer and its prognostic value
Authors: Shigematsu Hideo , Fujimoto Mutsumi , Kobayashi Yoshie , Yoshiyama Tomoyuki , Matsuura Noriaki , Komoto Daisuke , Kuraoka Kazuya
Published: May 2024

Objectives: We aimed to evaluate the effect of neoadjuvant chemotherapy (NAC) on peritumoral edema (PE) and its prognostic value in operable breast cancer.

Materials & Methods: This retrospective study included 128 cT1-4N0-3M0 breast cancer patients who underwent contrast-enhanced magnetic resonance imaging (MRI) of the breast before and after anthracycline- and/or taxane-based NAC, followed by curative surgery at our hospital, between 2006 and 2016. T2-weighted MRI revealed PE, and PE before NAC (pre-PE) and PE after NAC (residual PE) were evaluated. The correlation between the presence or absence of PE and relapse-free survival was evaluated using a log-rank test and multivariable Cox regression analysis. The risk of recurrence was stratified according to the residual cancer burden (RCB).

Results: Pre-PE was observed in 64 out of 128 patients (50%). Among 64 patients with pre-PE-positive breast cancer, residual PE was observed in 21 (32.8%). In the log-rank test, breast cancer with residual PE had a poorer prognosis than breast cancer with PE that had disappeared (p < 0.0001). In the multivariable Cox regression analysis, residual PE was a significant factor of poor prognosis (RR, 20.5; 95% confidence interval, 5.3–108.2; p < 0.0001). Regarding RCB stratification, compared to patients with breast cancer with disappeared PE, those with breast cancer with residual PE exhibited significantly poor prognosis in class II and class III (p = 0.006, 0.02).

Conclusion: In breast cancer with PE, residual PE after NAC is a significant factor related to poor prognosis.

Effect of neoadjuvant chemotherapy on peritumoral edema in patients with breast cancer and its clinical significance

XX XX

Citation Format: Hideo Shigematsu, Mutsumi Fujimoto, Yoshie Kobayashi, Tomoyuki Yoshiyama, Noriaki Matsuura, Daisuke Komoto, Kazuya Kuraoka. Effect of neoadjuvant chemotherapy on peritumoral edema in early stage breast cancer and its prognostic value [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-07-12.
Abstract PO3-10-06: Parenting While Living with Cancer - Providing Better Outcomes for Families During the Cancer Journey
Authors: Kabir Alicia
Published: May 2024

For over 20 years, Kesem has been dedicated to supporting children impacted by a parent’s cancer. To better understand the stresses on a family navigating cancer, Kesem completed a several month research program rooted in Diversity, Equity, and Inclusion (DEI) and consisting of ethnographic research, quantitative surveys, focus groups, benchmarking, and data analytics. We are using this research to develop a deeper understanding of the personal stories of families impacted by a cancer diagnosis and of the current data from experts in the field. Kesem is sharing our research findings in order for the general oncology space to better serve parents living with cancer.

The research included three weeks of ethnographic research completed in rural Mississippi, the Pacific Northwest, and southern Nevada. The research team completed 124 interviews in 18 cities, gathering deep insights about being a parent while living with cancer. The team also reviewed over 30 databases and conducted a survey of approximately 150 parents with cancer.

Little has been published about parental cancer in the past decade. Using literature reviews and data such as the 2020 decennial census, we have been able to generate a more accurate assessment of need than ever, confirming earlier estimates that there are approximately five million children in the United States who have a parent with cancer. This means that the average percentage of children under 18 who have experience with parental cancer is between 3.6%–5.5%.

The following key takeaways from this research are helpful for all who support patients, including oncologists, nurse navigators, and patient advocates:

Based on this research and our ongoing internal survey results, we know that patients generally have less anxiety when they know their children will receive a lifetime of support. Children who are supported are more likely to create a community of support for themselves, do better academically, and have increased mental health. This leads to better outcomes for the entire family.

Citation Format: Alicia Kabir. Parenting While Living with Cancer - Providing Better Outcomes for Families During the Cancer Journey [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-06.
Abstract PO3-12-04: Pulmonary Complication related to Trastuzumab Deruxtecan. A pharmacovigilance study from 2022-2023 FAERS Database
Authors: Neupane Niraj , Kharel Himal , Thapa Sangharsha
Published: May 2024

Background: The horizon of Trastuzumab Deruxtecan (T-DXd), an antibody-drug conjugate, has been expanding. After its promising results in HER2-positive/HER2-low Breast cancer, it has been on trial for other cancers, such as HER2-negative breast cancers, Gastrointestinal, lung, colorectal, urothelial, etc., and it has shown promising results in clinical trials. However, there have been reports of pulmonary adverse events associated with T-DXd, including interstitial lung disease (ILD) and pneumonitis. Understanding the occurrence and characteristics of these pulmonary complications is essential for optimizing patient care and ensuring the safe use of T-DXd. Using the FAERS (FDA Adverse Event Reporting System) database for 2022-2023 aims to see T-DXd-related pulmonary complications and guide healthcare professionals in monitoring and managing these adverse events effectively. Methods: We conducted a retrospective analysis of all reported cases of respiratory complications in patients using TDXD, utilizing data reported to the FDA Adverse Event Reporting System (FAERS) database for January 2022 to March 2023. We included patients of more than 18; these cases were identified and classified using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Results: In this study, a total of 296 cases of adverse events were reported in patients using TDXD. Among these cases, 74 (27%) were respiratory adverse events. The most frequently observed respiratory complications were interstitial lung disease (ILD) and pneumonitis, with 21 cases each, accounting for 56% of the total respiratory complications. Out of the 14 reported deaths in this cohort, pneumonitis was the most commonly seen respiratory complication, occurring in 8 patients, followed by pulmonary embolism and ILD, each reported in 4 patients. Conclusion: Respiratory complications were the most frequent among the reported adverse events, accounting for 27% of all cases. ILD and pneumonitis were the most common complications, with 14 deaths reported in this group. These findings underline the importance of closely monitoring and managing pulmonary adverse events in patients treated with T-DXd. Healthcare professionals can use this information to optimize patient care and ensure the safe use of T-DXd. However, it is important to note that this study was based on a database and has limitations such as underreporting bias and lack of a control group, which hinders establishing a causal relationship. Additional research is needed to identify risk factors and improve patient outcomes.

Citation Format: Niraj Neupane, Himal Kharel, Sangharsha Thapa. Pulmonary Complication related to Trastuzumab Deruxtecan. A pharmacovigilance study from 2022-2023 FAERS Database [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-04.
Abstract PO3-16-09: Real-World Experience with Trastuzumab Deruxtecan at a Diverse NCI Comprehensive Cancer Center
Authors: Meisel Jane , Ratcliffe Maisey
Published: May 2024

Background: Trastuzumab Deruxtecan (T-DXd) is an antibody-drug conjugate originally approved for use in patients with HER2–positive metastatic breast cancer (MBC). In June 2022, data from the DESTINY-Breast04 trial revealed a near-doubling of progression-free survival (PFS) and significantly improved overall survival (OS) for patients with HER2-low MBC (immunohistochemistry [IHC] grade 1+ or IHC2+ in situ hybridization [ISH]-negative) treated with T-DXd versus standard-of-care chemotherapy. The data from this clinical trial led to the approval of T-DXd for use in patients with HER2-low MBC. However, the DESTINY-Breast studies completed to date have included < 5% black patients. This retrospective study of patients at a racially diverse NCI Comprehensive Cancer Center was designed to study whether T-DXd in a real-world population are comparable to published data. Methods: A retrospective chart review was conducted and identified 72 patients with HER2-low and HER2-positive MBC who received T-DXd between December 2019 and March 2023 at the Winship Cancer Institute at Emory University. Data collected for all patients included demographics, prior breast cancer history, T-DXd -specific and post-T-DXd treatment, and clinical outcomes where applicable. Results: Of the 103 patients who were dosed with T-DXd, 55 (53.4%) had HER2-positive disease, and 48 (46.7%) patients had HER2-low disease. 71 (68.9%) patients had hormone-receptor positive disease and 32 (31.1%) patients had hormone-receptor negative disease. The overall study population was 46% Caucasian; 38% African American; 13% Asian; 4% Unreported. The average number of cycles received was 11 (on treatment an average of 8 months). Pneumonitis occurred in 5 patients (4.9%). HER2-positive patients were typically on T-Dxd for a greater number of cycles than HER2-low patients (Table 1). Additionally, patients with brain metastases were, on average, treated with T-Dxd longer than patients without brain metastases, 14.5 versus 9 cycles. The number of cycles of T-Dxd received, the need for dose reduction, and incidence pneumonitis did not differ significantly between black and white patients. The data for this study is preliminary 48% of the patient population are still actively undergoing T-Dxd treatment. Conclusion: This study reviewed and analyzed T-Dxd treatment in a diverse population of both HER2-positive and HER2-low MBC patients, and in this study, outcomes of treatment did not differ by race. More attention to this topic is needed in future studies of larger populations, along with increased efforts to enroll diverse patient populations in clinical trials.

Table 1.

Citation Format: Jane Meisel, Maisey Ratcliffe. Real-World Experience with Trastuzumab Deruxtecan at a Diverse NCI Comprehensive Cancer Center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-09.
Abstract PO3-18-07: Therapeutic Potential of Combining Eltanexor with Tamoxifen to Treat Primary and Metastatic Estrogen Receptor Positive (ER+) Breast Cancers
Authors: Jain Vedant , Kamdar Myra , McGee Hannah , Zuo Qianying , Yoo Jin Young , Landesman Yosef , Walker Christopher , Madak-Erdogan Zeynep
Published: May 2024

Estrogen receptors are key pathway initiators in the aggressive development of more than two-thirds of all breast cancers. Tamoxifen (TAM) is a selective estrogen receptor modulator that disables the ER pathway and inhibits the progression of ER+ breast cancer. Unfortunately, 10-40% of patients with ER+ breast cancer who were treated with TAM experience recurrence and metastasis within 10 years. We have previously identified exportin 1 (XPO1) to be more highly expressed in breast cancers with acquired TAM resistance compared to TAM-sensitive counterparts and showed that a combination treatment of TAM with an XPO1 inhibitor, selinexor, is an effective method of tumor suppression in preclinical models. In this study we investigated the activity of eltanexor, an investigational second generation XPO1 inhibitor with minimal penetration of the blood-brain barrier, to inhibit cancer growth without leading to weight loss. Our results show that mice harboring MCF7-ESR1Y537Sxenograft tumors had significantly less (P < .05) flank tumor growth when administered a treatment regimen of TAM and eltanexor compared to control mice. In metastatic tumor models, we observed decreased metastatic burden in mice harboring MCF7-ESR1 D538G and MCF7-ESR1Y537S tumors when co-administered TAM and eltanexor. We did not observe weight changes in either model. Our findings suggest that eltanexor may be a relevant treatment for further exploration in the context of a TAM combination therapy for treatment of ER+ breast cancer.

Citation Format: Vedant Jain, Myra Kamdar, Hannah McGee, Qianying Zuo, Jin Young Yoo, Yosef Landesman, Christopher Walker, Zeynep Madak-Erdogan. Therapeutic Potential of Combining Eltanexor with Tamoxifen to Treat Primary and Metastatic Estrogen Receptor Positive (ER+) Breast Cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-07.
Abstract PO3-22-12: Clinical feasibility of nipple sparing mastectomy (NSM) followed by immediate reconstruction based on direct-to-implant technique
Authors: Toh Uhi , Takao Yuko , Katagiri Yuriko , Sugihara Rie , Watanabe Hidetaka
Published: May 2024

[Background] The development of NSM approach combined with immediate implant-based breast reconstruction (IBBR) for patients with earlystage breast cancer (BC) preserve the natural skin envelope including nipple-areolar complex (NAC) to able to immediately reconstruct the breast with a permanent implant and simultaneously omit the skin expansion with a tissue expander. We retrospectively analyzed the clinical results of NSM+IBBR and compared the complication rate, outcome of patients who underwent immediate (one-stage) or delayed (two-stage) IBBR followed by standard TM or NSM.

[Patients and Results] A total of 108 patients who underwent a TM that included SSM or NSM followed by one- or two-stage IBBR between January 2013 and April 2022. 53 patients underwent a total mastectomy (TM) and 32 patients underwent an NSM followed by two-stage IBBR, and 24 patients underwent an NSM followed by one-stage IBBR. The operation times were 236, 247.2, and 321 min, and the mean surgical bleeding was 60.4, 88.8, and 138 ml, respectively. The complications in the three groups included infection (2.7%, 11.1%, and 6.3%), seroma/hematoma (0%, 5.6%, and 6.3%), flap necrosis (2.7%, 11.1%, and 12.5%), and loss of tissue expander or implant (2.7%, 5.6%, and 6.3%), respectively. At the median 62-month follow-up after the NSM + IBBR, one patient was diagnosed with distant lymph node metastases at the 24-month follow-up and one patient had new primary breast cancer within the reconstructed breast at the 38-month follow-up. But no loco-regional recurrence at the NAC or other distant recurrence were detected in the patients undergone regardless TM or NSM + one-stage or two-stage IBBR.

[Summary] Our results suggested that the use of one-stage IBRR tended to increase the operating time and the amount of bleeding compared to two-stage IBRR and the complication rate might be higher in cases in which an NSM is followed by IBBR. Oncological outcome was consistent with the studies showing that loco-regional recurrence is less likely at the NAC regardless of whether the patients underwent one-stage or two-stage IBBR following an NSM.

Citation Format: Uhi Toh, Yuko Takao, Yuriko Katagiri, Rie Sugihara, Hidetaka Watanabe. Clinical feasibility of nipple sparing mastectomy (NSM) followed by immediate reconstruction based on direct-to-implant technique [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-12.
Abstract PO3-28-03: Mitigating Financial Toxicity Through Individualized Education
Authors: Doran Joanna , Bryant Monica
Published: May 2024

Background Triage Cancer® offers a free Legal & Financial Navigation Program (LFN) that supports individuals coping with cancer, their caregivers, and health care providers as they navigate the legal and practical matters that arise after a diagnosis. Without access to the proper resources, individuals impacted by cancer may suffer the financial burden of a diagnosis – or financial toxicity, as coined by researchers at Duke. Financial toxicity has proven to have a negative impact on quality of life and mental and physical health of individuals coping with cancer. The LFN provides individuals impacted by a diagnosis with the accurate information and resources needed to help mitigate financial toxicity. The LFN addresses the gap in education around cancer-related legal issues to improve the overall health of individuals coping with cancer. This tailored education is particularly important for providers, as there is a significant lack of training around cancer-related legal issues. Consequently, health care providers are often not equipped to answer their patient’s complex questions about cancer-related legal issues, including health insurance, disability insurance, and employment. The LFN provides personalized education on relevant laws and actionable steps to navigate the situation, which improves the provider’s ability to support their patients and the patients’ ability to self-advocate. Methods To start the process, individuals complete a brief intake form online and schedule a call with the staff. During the call, the staff provides education around relevant laws and practical options to manage the situation. The efficacy of the program is measured through voluntary survey response. Callers receive a follow-up email with a one question survey within a day of the initial call. After three weeks, the caller also receives a detailed survey. Results In 2022, Triage Cancer® provided direct consultation to 1,289 callers; 384 with breast cancer. For those callers, the most common topics included: employment, disability insurance, and health insurance. Survey data indicates that after speaking with staff, 93% felt better prepared with regard to their options and 94% agreed that they had actionable next steps. Conclusion The LFN provides tailored education around cancer-related legal issues in order to improve the quality of life of individuals coping with cancer. The LFN provides accurate information on relevant laws and actionable steps to help individuals make informed decisions to mitigate financial toxicity.

Citation Format: Joanna Doran, Monica Bryant. Mitigating Financial Toxicity Through Individualized Education [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-03.
Abstract PO3-28-12: Targeting the KCa3.1 potassium channel arrests ER+ breast cancer growth and re-sensitizes to drug resistance
Authors: Delisi Davide , Cetin Metin , Saatci Ozge , Sahin Ozgur , Gentile Saverio
Published: May 2024

Standard of care for breast cancer (BC) treatment including Selective-Estrogen Receptor (ER)-modulators and/or degraders (SERM; tamoxifen, SERD;Fulvestrant) or cyclin-dependent kinases CDK4 and CDK6 (palbociclib) can be effective therapeutic strategies. However, drug toxicity and/or drug resistance severely limit these approaches and patients succumb to the disease. Therefore, there is an urge to develop new therapeutic strategies against ER+-BC. Ion channels are general pharmacological targets however, little is known about the role of this class of proteins in cancer biology. We discovered that expression of the KCa3.1 potassium ion channel is downregulated in ER+-BC. Also, patients expressing high level of KCa3.1 present a better overall survival (OS) and relapse free survival when compared with patients with low expression. Thus, these data indicate that KCa3.1 is a prognostic factor in ER+-BC and that high activity of this channel plays a fundamental role in an oncosuppressor signature. Our central hypothesis is that pharmacological targeting KCa3.1 with activator molecules arrests growth of ER+-BC. We discovered that ER+-BC patient-derived organoids (PDO) and cell lines treated with KCa3.1 agonists including the FDA approved Chlorzoxazone, (CZX) arrests significantly inhibit tumor growth. Activation of KCa3.1 arrested the cell cycle in the G0/G1 phase by activating a senescent-like phenotype. Furthermore, our studies on the biochemical signaling that underlines this event demonstrated that increased expression level of KCa3.1 protein associated with lower expression level of ERa in a cell cycle phase-dependent manner. Furthermore, use of KCa3.1activator produced a proteasomal-dependent ERa degradation. To better characterize the therapeutic benefit of targeting the KCa3.1, we assessed the effects of CZX on developed several tamoxifen and/or palbociclib resistant cell lines and PDO models. We found that the combination of CZX strongly potentiated the lethal effects of both tamoxifen and palbociclib in the relative resistant models. We conclude that pharmacological targeting KCa3.1 potassium channel in ER+-BC can be considered a novel, safe and efficacious therapeutic strategy.

Citation Format: Davide Delisi, Metin Cetin, Ozge Saatci, Ozgur Sahin, Saverio Gentile. Targeting the KCa3.1 potassium channel arrests ER+ breast cancer growth and re-sensitizes to drug resistance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-12.
Abstract PO3-29-02: Single Nucleotide Polymorphisms (SNPs) in Inflammatory Pathways Associated with Body Mass Index (BMI) and Breast Cancer (BC) Risk: A Scoping Review
Authors: Quinn Erina , Wekwerth Braelyn , Doyle Maya , Carlos Ruth
Published: May 2024

Background: BMI is a risk for BC, with inflammation as a possible link. We conducted a scoping review assessing SNPs in inflammatory pathways posited to modify BC risk by BMI. Design: We followed PRISMA guidelines for scoping reviews. Pubmed, Medline and OVID databases were interrogated for publications between 1/2000-12/2023 using search terms “breast cancer” AND [BMI OR “body mass index” OR elevated BMI OR obesity] AND [SNP OR “single nucleotide polymorphism” OR polymorphism OR mutation] AND [inflammation OR cytokines OR IL-1 OR IL-2 OR IL-4 OR IL-6 OR IL-8 OR IL-10 OR IL-12 OR TNF-A or TGFB OR CRP]. A single reviewer assessed 67 unique publications and determined that 17 met inclusion criteria as a case control or cohort study. Two reviewers extracted the following data: demographics, SNP, number of cases and controls by BMI. Disagreements were resolved by consensus with a third reviewer. High BMI was defined by each study using accepted levels within their population: ≥25 (United States, Mexico) or ≥22 (Korea). Unadjusted odds ratios (OR) for BC risk were calculated by SNP stratified by BMI. Results: Data were extractable from 5 studies, all case controls. We requested patient level data for 12 studies from the corresponding author, without response. When stratified by BMI, we detected heterogenous effects of SNPs on BC risk (Table 1, only significant or trending correlations presented). With high BMI, IL-1β-31 TT (OR 2.19, 0.86-5.59) and GC/CC (OR 0.81, 0.68-0.97) correlated with BC risk (p < 0.05). With normal BMI, STAT3 rs1026916 GA (OR 0.78, 0.62-0.96) and JAK2 rs1536800 TT (OR 1.93, 1.07-3.48) correlated with BC risk. Additional SNPs trended to correlate with BC risk (0.05 < mo >≤">≤ p < mo >≤">≤ 0.10) by BMI. Conclusion: The association of inflammatory SNPs and BC risk is complex and can be both protective and predisposing to BC risk, with BMI modifying SNP risk. Future research can assess SNPs and BC risk in more diverse populations.

Citation Format: Erina Quinn, Braelyn Wekwerth, Maya Doyle, Ruth Carlos. Single Nucleotide Polymorphisms (SNPs) in Inflammatory Pathways Associated with Body Mass Index (BMI) and Breast Cancer (BC) Risk: A Scoping Review [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-29-02.
Abstract PO3-29-03: An Emerging Class of ER mutations Enhances ER Dimerization and Promotes ER Activity
Authors: Irani Seema , Tan Wuwei , Li Qing , Toy Weiyi , Jones Catherine , Gadiya Mayur , Marra Antonio , Katzenellenbogen John , Carlson Kathryn , Katzenellenbogen Benita S. , Shen Yang , Chandarlapaty Sarat
Published: May 2024

Physiological activation of estrogen receptor alpha (ERα) requires the binding of estradiol (E2) to the ligand binding domain (LBD) of the receptor. This interaction triggers a repositioning of helix 12 (H12), facilitating the recruitment of coactivator proteins to the unoccupied coactivator binding groove. However, in the context of breast cancer, point mutations of ERα at H12 lead to its repositioning and self-activation in the absence of E2.

Through MSK clinical sequencing breast cancer cohort (MSK-IMPACT), we assayed 8302 samples of ER+ breast cancer patients and identified 649 mutations within the LBD of ERα. 471 of these mutations (73%) were located at H11-H12 loops (D538, Y537, L536), while the remaining 27% were located near the dimer interface of ERα (V422, G442, F461, S463P, L469). Through in vitro biochemical and cell assays, we identified that these mutations promote dimer formation and hormone-independent transcriptional activity. Tumors expressing these mutations exhibited significantly accelerated growth compared to their wild-type controls. Unlike Y537S, cells harboring mutations at the dimer interface maintain their sensitivity to Selective Estrogen Receptor Degraders (SERDs), including Fulvestrant, recently FDA-approved Elacestrant, and Camizestrant, as well as Selective Estrogen Receptor Modulators (SERMs) including Tamoxifen and Raloxifene. By utilizing machine learning and computational structural analyses, we uncovered that these mutants, unlike Y537 repositions H12, act distinctly through conformational change across the ERα dimer interface. Further cell assays proved that the dimerization leads to increased stability of the receptor and facilitates its nuclear localization, which is required for ERα activation.

Collectively, our finding unveiled a new class of ER mutations that enforce receptor dimerization and activation of the ER signaling pathway. The discovery opens up a new therapeutic interventional possibility, suggesting that targeting dimerization could emerge as a new strategy to combat these malignancies.

Citation Format: Seema Irani, Wuwei Tan, Qing Li, Weiyi Toy, Catherine Jones, Mayur Gadiya, Antonio Marra, John Katzenellenbogen, Kathryn Carlson, Benita S. Katzenellenbogen, Yang Shen, Sarat Chandarlapaty. An Emerging Class of ER mutations Enhances ER Dimerization and Promotes ER Activity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-29-03.