Adjuvant Therapy For Breast Cancer Research Articles

Breast Cancer Adjuvant Radiotherapy in Up-Front to Chemotherapy: Is There a Worthwhile Benefit? A Preliminary Report.

We administered a new breast cancer (BC) adjuvant therapy sequence that delivered postoperative radiotherapy (PORT) before chemotherapy (CT). Our aim was to assess the gain in time to start PORT and the G2-G3 acute-subacute toxicity rate of whole breast adjuvant hypofractionated radiotherapy (AH-RT) administered up-front to the third-generation adjuvant CT (A-CT) in high-risk nodal positive BC in a preliminary report at 2 years. This retrospective study analysed the duration of treatment and safety of AH-RT administered up-front to A-CT in high-risk nodal positive BC patients (pts). Data on 45 pts treated between 2022-2023 were collected. All pts underwent the third-generation A-CT after AH-RT 15-5 fractions with or without a boost. Acute toxicity was scored according to CTCAE v5.0 for skin, pulmonary, and cardiac adverse events. Univariate and multivariate analyses were conducted to assess significant prognosticators for skin/lung/heart acute toxicities in the AH-RT 5-15 fractions arms and CT (p < 0.005). A reduction in the time to PORT initiation and overall adjuvant treatment time was recorded. RT was initiated 5 median weeks after surgery, and A-CT was performed 9 median weeks after surgery. The median duration of the entire adjuvant treatment was 35 weeks after surgery. At 6 months mean follow-up, no significant differences in G2-G3 toxicity were noted between the different hypofractionated RT arms, irrespective of the CT schedules, irradiated volumes, or boost (SIB or sequential) in univariate and multivariate analyses. In the multivariate analysis, no significant effects in CT schedules and AH-RT 5-15 arms for skin/lung acute toxicities (p = 0.077 and p = 0.68; 0.67 and 0.87, respectively) were recorded. As a new PORT approach in BC, AH-RT up-front to the third-generation A-CT appeared safe with a low acute toxicity profile, providing an advantage in shortening the time from surgery to PORT initiation and the overall adjuvant treatment time.

Selecting postoperative adjuvant systemic therapy for early-stage breast cancer: An updated assessment and systematic review of leading commercially available gene expression assays.

Gene expression assays (GEAs) can guide treatment for early-stage breast cancer. Several large prospective randomized clinical trials, and numerous additional studies, now provide new information for selecting an appropriate GEA. This systematic review builds upon prior reviews, with a focus on five widely commercialized GEAs (Breast Cancer Index®, EndoPredict®, MammaPrint®, Oncotype DX®, and Prosigna®). The comprehensive dataset available provides a contemporary opportunity to assess each GEA's utility as a prognosticator and/or predictor of adjuvant therapy benefit.

Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial.

LBA1001 Background: The combination of CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard first line treatment for HR+, HER2- advanced breast cancer (ABC). While disease progression occurs in nearly all patients (pts) with ABC, the optimal treatment for pts who experience progression on a CDK4/6i + ET remains uncertain. Real-world evidence suggests that use of abemaciclib after disease progression on a prior CDK4/6i prolongs progression-free survival (PFS) in ABC; however, Phase 2 trials with other CDK4/6i have generated mixed results. Here we present the primary outcome analysis for the Phase 3 postMONARCH trial (NCT05169567) of fulvestrant + abemaciclib or placebo in pts with HR+, HER2- ABC following disease progression on prior CDK4/6i + ET. Methods: postMONARCH was a global, double-blind, placebo-controlled study with pts randomized 1:1 to abemaciclib + fulvestrant or placebo + fulvestrant. Eligible pts had disease progression on a CDK4/6i + AI as initial therapy for ABC or relapse on/after a CDK4/6i + ET as adjuvant therapy for early breast cancer. No other prior treatment for ABC was permitted. Primary endpoint was investigator-assessed PFS; secondary endpoints included PFS by blinded independent central review (BICR), overall survival (OS), objective response rate (ORR), and safety. Assuming a hazard ratio (HR) of 0.7, the study had ~80% power to detect superiority for abemaciclib, with a cumulative 2-sided type I error of 0.05. Kaplan-Meier method was used to estimate PFS curves and treatment effect was estimated using a stratified Cox proportional hazard model. Results: A total of 368 pts were randomized to abemaciclib + fulvestrant (n = 182) or placebo + fulvestrant (n= 186). Most pts (99%) enrolled directly after CDK4/6i + ET as initial therapy for ABC. Prior CDK4/6i was 59% palbociclib, 33% ribociclib, and 8% abemaciclib. At interim analysis, the study reached the pre-specified criteria for significantly improved investigator-assessed PFS with abemaciclib + fulvestrant compared to placebo + fulvestrant (169 events, HR = 0.66; 95% CI 0.48 – 0.91; p = 0.01). At primary analysis (258 events), the HR was 0.73 (95% CI 0.57 – 0.95), with PFS rates at 6 months of 50% vs 37% for the abemaciclib and placebo arms, respectively. Consistent effect was seen across major clinical and genomic subgroups, including pts with baseline ESR1 or PIK3CA mutations. ORR was improved with abemaciclib compared to placebo (17% vs 7%, respectively, in pts with measurable disease). PFS according to BICR was also improved with HR = 0.55 (95% CI 0.39 - 0.77). OS remains immature (20.9% event rate). Safety was consistent with the known profile of abemaciclib. Conclusions: Abemaciclib + fulvestrant demonstrated statistically significant PFS improvement in pts with ABC progression on prior CDK4/6i-containing therapy. Clinical trial information: NCT05169567 .

Mammary Paget’s Disease as a Sign of Local Recurrence Two Decades Following Breast Conservation and Adjuvant Therapy for Early Stage Breast Cancer

Mammary Paget’s Disease as a Sign of Local Recurrence Two Decades Following Breast Conservation and Adjuvant Therapy for Early Stage Breast Cancer

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-β dual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen in vitro, which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-β in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application.

Impact of semaglutide and tirzepatide administration on weight in women with stage I-III breast cancer.

e24140 Background: Weight gain and obesity are significant problems for women receiving adjuvant therapy for breast cancer and obesity is associated with adverse breast cancer outcomes. In addition, obesity is associated with negative impact on overall physical and mental health. The GLP-1 agonists, semaglutide (S) and tirzepatide (T), are effective in achieving weight loss and have been associated with decreased incidence of diabetes, stroke and overall mortality in the non-diabetic as well as diabetic populations. There are limited data on the efficacy and safety of GLP1 agonists in women with breast cancer. Methods: We performed a retrospective analysis of the association of S and T use with weight loss in patients with stage I-III breast cancer diagnosed and treated at the Yale Cancer Center/Yale New Haven Health Network between 2017 and 2022. After institutional review board approval, a database including 7149 patients including 92,989 office visits was constructed. Maximal weight loss after S/T prescription as well as mean weight loss were calculated. S and T treated patient’s stage distribution and rates of recurrence were compared to untreated patients. For patients without metastatic disease, repeated measures regression analysis was utilized to evaluate changes in weight and BMI. Results: Of the 5430 evaluable patients with non-metastatic disease, 70 (1.3%) were prescribed S or T. Mean age was 58 (41-78). 74% received endocrine therapy. Mean pretreatment weight was 95.8 kg and BMI was 35.9 kg/m2. Mean weight loss for S/T treated patients was 3.03 kg (3.9-2.13, p &lt; .0001) corresponding to reduction in BMI of 1.1 kg/m2 (0.7-1.5 p &lt; .0001). We also calculated maximal weight loss after S/T prescription. Mean maximal weight loss was 8.89 kg (6.71-10.98 P &lt; .0001) corresponding to a mean maximal reduction in BMI of 3.2 kg/m2 (2.3-4.2 P &lt; .0001). Rates of local, locoregional, and distant breast cancer recurrence were 1.5%, 0%, 1.5% in the S/T treated patients and 1.3%, 4.7% and 3.3% in the untreated patients. None of these differences were statistically significant. Conclusions: In this retrospective analysis, GLP-1 agonist are associated with clinically meaningful weight loss in overweight and obese women with early breast cancer. Recurrence risk did not appear to be preliminarily impacted by treatment. Additional research is needed on long term safety as well as weight loss maintenance with these drugs in breast cancer survivors.

Adherence to adjuvant hormone therapy in hormone-sensitive breast cancer: Insights from the Medical Oncology Department at Hassan II University Hospital, Morocco.

e12505 Background: Adjuvant endocrine therapy (AET) improves long-term survival for hormone-sensitive breast cancer; However, suboptimal adherence is prevalent, with many women failing to follow prescribed dosage and frequency. Long-term adherence patterns to AET are poorly understood. Additionally, there is a lack of data regarding the adherence to AET among Moroccan women and the factors that may influence it. Objectives: The primary objective of the study was to assess the adherence rate to AET in patients with HR-positive early breast cancer being treated at Hassan II University Hospital of Fez, Morocco. Secondary objectives included determining factors associated with poor adherence and assessing the adverse events associated with AET and their prevalence. Methods: We conducted a cross-sectional study involving 335 breast cancer patients undergoing AET. Eligible patients, who had received at least one dispensing of AET, participated in the study through a direct questionnaire survey after providing signed consent. The questionnaire comprised sections covering patient demographics, clinical data (stage, type of AET, duration of therapy), side effects or symptoms related to AET, other factors that may impact adherence. Adherence to AET was assessed at three points of measurement: 1 year, 3 years, and ≥ 5 years after the initiation of therapy. The study was carried out with respect to the Moroccan regulation in effect. Results: The study included 335 cases with an average age of 54 years. Participants were predominantly illiterate (62%) and post-menopausal (50.7%). Most were classified as stage II UICC (53.5%). Mastectomy was performed in the majority (74%). Neo(adjuvant) CMT was given to 79.4%, and adjuvant radiotherapy to 86.9%. Tamoxifen was administered to 55.4%, and aromatase inhibitors to 44.6%. Medical castration was associated with 12.5%, and 35 patients switched AET over time. Only 12.8% exceeded 5 years of AET during recruitment. Adherence assessment revealed an overall adherence rate of 53.4%. Notably, 67.2% claimed never to forget their medication, and about 20% temporarily stopped it, primarily due to lack of information. Most participants used a reminder strategy, notably alarms (43.3%). Treatment tolerance varied, with hot flushes and arthralgia being predominant side effects. Statistical analyses found a significant link between treatment lasting over 5 years and non-adherence (p = 0.003). However, the use of an alarm as a reminder strategy strengthened adherence (p = 0.021). No statistically significant differences were noted in other variables. Conclusions: Despite the benefits, ensuring adjuvant hormone therapy adherence is challenging. Our analysis, estimating a 53.4% global adherence, found that only treatment duration and recall strategy significantly correlated with adherence.

Ultra-hypofractionated adjuvant radiation therapy for breast cancer (UK FAST-Forward trial): A real life scenario analysis in a developing country.

e12501 Background: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The FAST-Forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published.

Exploring factors impacting quality of life in patients with breast cancer undergoing adjuvant hormone therapy: Experience of the Medical Oncology Department-CHU Hassan II-FEZ University Hospital.

e12507 Background: Considering that the recommended duration of adjuvant hormone therapy in localized breast cancer is at least 5 years, it becomes crucial to investigate the quality of life (QOL) of these patients and the factors influencing it. Objectives: To assess the quality of life (QOL) and identify factors impacting it in patients with localized hormone-sensitive breast cancer receiving adjuvant hormone therapy. Methods: We surveyed 335 patients with localized hormone-sensitive breast cancer undergoing adjuvant hormone therapy using the Moroccan Arabic dialect version of the EORTC QLQ-C30 questionnaire. Written informed consent was obtained from all participants. Confidentiality of participant data was maintained. The study was carried-out with respect to the Moroccan regulation in effect. Results: The overall quality of life (QOL) in our patient population was moderate, with positive scores for social functioning, followed by physical, cognitive, and emotional functioning. Financial difficulties emerged as the most influential factor affecting patients' QOL, followed by fatigue, pain, and other symptoms. Age-related declines in physical functioning were observed, with symptoms more prevalent, especially diarrhea, in patients aged 70 and above (p = 0.009). Urban patients faced a greater financial impact on QOL than rural patients (p = 0.025). Higher education correlated with improved QOL, particularly in physical functioning (p = 0.025). Married individuals demonstrated better overall QOL and fewer symptoms (p = 0.027). Menopausal patients exhibited lower ability and a higher loss of appetite (p = 0.027). No significant correlation was found between UICC stage and QOL. Patey-mastectomy was associated with more pain than tumorectomy (p = 0.024). Previous chemotherapy had no overall QOL impact, but users reported less diarrhea (p = 0.016). Hormone therapy type did not significantly affect overall health status, except for tamoxifen users who demonstrated improved functional roles (p = 0.008). The duration of adjuvant hormone therapy (&lt;5 years or &gt;5 years) showed no significant difference in patient QOL. Associated castration had a significant impact on overall health and role functioning, favoring non-castration (p = 0.034 and p = 0.011). Effective treatment tolerance positively influenced overall QOL, leading to better physical, emotional, and cognitive functioning (p &lt; 0.0001), with fewer pronounced symptoms. Conclusions: Our study indicate that the overall QOL of patients with localized breast cancer under AET was moderate, and several factors were identified as major influences, each affecting the QOL in distinct ways.

Escalation of adjuvant endocrine therapy for early hormone-dependent HER2-negative breast cancer: to whom, when and why?

This review presents the evolution of adjuvant endocrine therapy for early hormone-dependent HER2-negative breast cancer, describes late relapse phenomenon, provides clinical rationale for escalation of treatment, analyzes the key stages of the metastatic cascade, and provides a scientific rationale for the introduction of CDK4/6 inhibitors into adjuvant treatment regimens. The main results of two large randomized studies of therapy including abemaciclib (MonarchE) and ribociclib (NATALEE) in patients with early stages of hormone-dependent HER2-negative breast cancer are presented; the oncological results of escalation of treatment and the safety of therapy are assessed.

Choice of adjuvant therapy for HER2-positive breast cancer in real clinical practice: analysis of physician preferences in the Russian Federation

Adjuvant therapy with trastuzumab made a significant contribution to improving disease-free and overall survival rates in patients with HER2-positive breast cancer. However, in a number of clinical situations the risk of disease recurrence remains increased. Carrying out neoadjuvant treatment followed by post-neoadjuvant therapy, depending on the degree of pathomorphological response, is the modern standard, allowing to cure a significantly larger number of patients. This became possible thanks to the expansion of the arsenal of terget anti-Her drugs and the introduction into real clinical practice of double anti-HER2 blockade (trastuzumab + pertuzumab) and an antibody conjugate with a cytostatic drug – trastuzumab emtansine. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of HER2-positive breast cancer” was conducted. The survey involved 50 specialists from different regions of the country who are directly involved in developing a treatment plan for patients, which allows them to reflect the preferences of leading chemotherapists regarding tactics for HER2-positive breast cancer. This publication reflects the results of part of the survey, devoted to the choice of adjuvant and post-neoadjuvant therapy for HER2-positive breast cancer. Identified a clear positive trend in favor of neoadjuvant treatment followed by post-neoadjuvant therapy using modern targeted drugs such as pertuzumab and trastuzumab emtansine. The survey results show that 68% of patients with RCB-II–III residual tumor receive post-neoadjuvant trastuzumab emtanzine, in 2021 this figure was only 24%. The absolute majority of patients who have not received neoadjuvant therapy, but have N2–3 stage, receive double anti-HER2 therapy with trastuzumab + pertuzumab in the adjuvant setting. High adherence to the therapy was noted, as 97% of patients complete the planned course of T-DM1, and 91.2% of patients complete a year of adjuvant anti-HER2 therapy. These figures are noticeably higher than the indicators of registration studies. Issues of effectiveness come to the fore in choosing therapy. Issues of drug availability remain relevant, but are not decisive. The survey also revealed factors that were not obvious at first glance and influenced treatment results.

Nutritional support in the complex of medical rehabilitation at the stage of adjuvant radiation therapy of breast cancer

BACKGROUND: Currently it is known that there exists the need for complex medical rehabilitation at the stage of adjuvant radiation treatment of breast cancer. However, data on the combined use of nutritional support and physical factors at this stage of oncological treatment are not available. AIM: Evaluation of the effectiveness of specialized therapeutic and preventive nutrition in patients with malignant breast diseases and a history of polychemotherapy at the stage of adjuvant radiation therapy in complex medical rehabilitation using low-temperature plasma and general magnetic therapy. MATERIALS AND METHODS: A prospective simple randomized study was conducted, which involved 60 patients at the stage of adjuvant radiation therapy for breast cancer. The main group (n=30) received a course of medical rehabilitation with the inclusion of nutritional support using specialized therapeutic and preventive nutrition LEOVIT ONCO®, as well as exposure to low-temperature plasma and general magnetotherapy. In the comparison group (n=30), the rehabilitation course included general magnetic therapy without therapeutic and preventive nutrition. All patients underwent individual physiotherapy exercises, and sessions with a medical psychologist. The results obtained were recorded using clinical and functional, laboratory, instrumental studies. RESULTS: It has been established that the use of specialized dietary products LEOVIT ONCO and physical factors is an effective method of rehabilitation. The use of nutritional support demonstrates the maintenance of the patient’s protein status, reduces intoxication, and reduces the negative impact of oxidative stress factors in the body at the stage of adjuvant radiation treatment. The inclusion of low-temperature plasma and general magnetic therapy in the rehabilitation program has a beneficial effect on hemomicrocirculation in the area of ionizing radiation exposure. CONCLUSION: The use of nutritional support and physical factors, as a component of complex medical rehabilitation, helps to maintain the optimal nutritional status of the patient, reduces the manifestations of skin radiation reactions, improves the psycho-emotional state of patients and the quality of life of patient.

Preexisting Diabetes and Breast Cancer Treatment Among Low-Income Women

Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain. To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer. This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023. Preexisting diabetes. Logistic regression was used to estimate odds ratios (ORs) of utilization (yes/no), timely initiation (≤90 days postsurgery), and completion of radiotherapy and chemotherapy, as well as adherence (medication possession ratio ≥80%) and persistence (<90-consecutive day gap) of endocrine therapy in the first year of treatment for women with diabetes compared with women without diabetes. Analyses were adjusted for sociodemographic and tumor factors. Among 3704 women undergoing definitive surgery, the mean (SD) age was 51.4 (8.6) years, 1038 (28.1%) were non-Hispanic Black, 2598 (70.1%) were non-Hispanic White, 765 (20.7%) had a diabetes history, 2369 (64.0%) received radiotherapy, 2237 (60.4%) had chemotherapy, and 2505 (67.6%) took endocrine therapy. Compared with women without diabetes, women with diabetes were less likely to utilize radiotherapy (OR, 0.67; 95% CI, 0.53-0.86), receive chemotherapy (OR, 0.67; 95% CI, 0.48-0.93), complete chemotherapy (OR, 0.71; 95% CI, 0.50-0.99), and be adherent to endocrine therapy (OR, 0.71; 95% CI, 0.56-0.91). There were no significant associations of diabetes with utilization (OR, 0.95; 95% CI, 0.71-1.28) and persistence (OR, 1.09; 95% CI, 0.88-1.36) of endocrine therapy, timely initiation of radiotherapy (OR, 1.09; 95% CI, 0.86-1.38) and chemotherapy (OR, 1.09; 95% CI, 0.77-1.55), or completion of radiotherapy (OR, 1.25; 95% CI, 0.91-1.71). In this cohort study, preexisting diabetes was associated with subpar adjuvant therapies for breast cancer among low-income women. Improving diabetes management during cancer treatment is particularly important for low-income women with breast cancer who may have been disproportionately affected by diabetes and are likely to experience disparities in cancer treatment and outcomes.

Royal jelly and its hormonal effects in breast cancer: a literature review.

Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer. Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included. According to the collected preclinical data, consumption of royal jelly at daily doses below 200mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells. Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

Abstract PO3-02-14: The Safety of Breast Reconstruction: The Impact of Breast Reconstruction Surgery on Postoperative Adjuvant Therapy for Breast Cancer

Abstract Background: Postoperative adjuvant therapy is very important in treating breast cancer, and increasing numbers of patients are undergoing immediate breast reconstruction (IBR) at the same time as breast cancer surgery. However, the impact of breast reconstruction surgery on adjuvant therapy is controversial. In this multicenter cohort study led by the Japanese Breast Cancer Society, we examined the impact of reconstructive surgery on postoperative adjuvant therapy in breast cancer patients who underwent IBR. Methods: We examined the association between adjuvant therapy and complications of reconstructive surgery in 4726 patients with primary breast cancer who underwent IBR during the period from January 1, 2008 to December 31, 2016. Statistical analysis employed the χ2 test. Results: Of the 995 patients who received adjuvant chemotherapy, the median time from the date of surgery to the start of chemotherapy was 51.0 days, with 63 patients (6.2%) starting more than 90 days after surgery. Eighty-four IBR complications required surgery (8.4%), including infections and tissue expander (TE) removal. Of the 63 patients for whom chemotherapy was initiated 90 days or more after surgery, 10 patients (15.9%) had complications requiring surgery, significantly more than the 74 patients (7.9%) in the &amp;lt; 90 days group (P = 0.028). Post-mastectomy radiation therapy (PMRT) was performed after breast cancer surgery in 359 cases: 69 cases received autologous tissue irradiation, 46 TE irradiation, 241 silicone breast implant (SBI) irradiation, and 3 artificial material removal before irradiation. 5 cases given autologous tissue irradiation and 26 receiving artificial material irradiation (22 of whom the artificial material was removes) required surgery within 1 year after the cancer surgery due to complications of IBR. There was no significant difference in the frequency of complications requiring surgery between autologous tissue irradiation and artificial material irradiation (P=0.632). There were 33 complications (9.2%) requiring surgery in the irradiated group, significantly more than the 129 cases (3.0%) in the non-irradiated group (P&amp;lt; 0.001). Conclusion: Adjuvant chemotherapy was generally not delayed, but complications requiring surgery related to IBR were more frequent in those with delay beyond 90 days, suggesting that postoperative complications from breast reconstruction may have influenced the delay in initiating chemotherapy. Therefore, in cases for whom postoperative chemotherapy is anticipated, complications from breast reconstruction may have impacted outcomes, making preoperative risk assessment even more important. There was no difference in the frequency of reconstructive complication surgery according to whether autologous tissue irradiation or artificial material irradiation had been used, but further investigation is needed. Citation Format: Naomi Nagura, Akiko ogiya, Hiroko Nogi, Kazutaka Narui, Hiroki Mori, Shinsuke Sasada, Makoto Ishitobi, Naoto Kondo, Chikako Yamauchi, Ayaka Shimo, Miho Saiga, Hirohito Seki, Teruhisa Sakurai, Tadahiko Shien. The Safety of Breast Reconstruction: The Impact of Breast Reconstruction Surgery on Postoperative Adjuvant Therapy for 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 PO3-02-14.

Abstract PO4-20-03: HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13)

Abstract Background: In estrogen receptor (ER)-positive human epidermal growth factor receptor2 (HER2)-negative early breast cancer (EBC) patients, NCCN treatment guideline recommend 21-gene tests for decision of adjuvant chemotherapy if tumor size is over 0.5cm or node positive disease. In addition, GenesWellTM BCT is a prognostic assay that predict the risk of recurrence in patients with ER-positive HER2-negative and nodal stage 0-1 EBC. According to gene tests, EBC patients with high recurrence risk would have help from adjuvant chemotherapy to increase the rate of disease free survival but toxicities of chemotherapy are not negligible. Therefore, the effort for escaping adjuvant chemotherapy has been performed and currently CDK4/6 inhibitor would be considered as the substitute for cytotoxic chemotherapy in ER-positive HER2-negative EBC patients. Methods: HIPEx trial is a multi-center, phase II clinical trial to determine the efficacy of adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative EBC with high recurrence score according to GenesWellTM BCT (NCT04247633). Eligible patients are women who received curative surgery and diagnosed as ER-positive, HER2-negative and pathologic stage T1b-T2 and/or N0-1. Clinical recurrence risk is high according to the modified Adjuvant! Online guideline and GenesWellTM BCT score is 4 or more which being genomic high risk. Other criteria include ECOG performance status ≤1, adequate organ functions and availability of an archival surgical specimens. Patients receive palbociclib 125mg once daily for 21 days of 28-day cycle plus tamoxifen or aromatase inhibitor (anastrozole, letrozole or exemestane) once daily for every day. Palbociclib would be taken for two years and endocrine therapy for five years or more. If adjuvant radiotherapy is required, palbociclib should be taken two weeks after the end date of radiotherapy. If patients are premenopausal status, GnRH agonist is allowed. Primary endpoint is 3-year event free survival (EFS) rate of high clinical and genetic risk ER-positive EBC. Secondary endpoints include 3-year overall survival, quality of life, safety and tolerability of palbociclib with endocrine therapy as an adjuvant setting, exploratory analysis of predictive and prognostic biomarkers and the performance of GenesWellTM BCT for 3-year EFS rate. In total, 578 patients would be enrolled in this trial. Based on the previous results of GenesWell™ BCT in Korea, the 3-year EFS rate for the past control group (chemotherapy followed by endocrine therapy) is 87.0% and the treatment group in this clinical trial is assumed to be 90.5%.(hazard ratio for EFS = 0.717). Null hypothesis is the 3year-EFS rate in patients received adjuvant palbociclib and endocrine therapy is not less than that of the past control group. Alternative hypothesis is the 3year-EFS rate of this trial is less than that of the past control group (one-sided). Significance level is 0.025, power is 0.80. Considering 10% drop out rate, 4-years of accrual patient enrollment and 3-years of follow up period, 578 patients were required in this clinical trial. Citation Format: Ji-Yeon Kim, Sung Hoon Sim, Jieun Lee, In Hae Park, Kyong Hwa Park, Seock-Ah Im, Jee Hung Kim, Kyoung Eun Lee, Jeong Eon Lee, Jai Min Ryu, Young Kee Shin, Yeon Hee Park. HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13) [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 PO4-20-03.

Abstract PO2-07-04: Applying the Alliance Trial Guidelines in Multi-focal Breast Disease Using an Artificial Intelligence Computational Platform: Economic Analysis and Cosmetic Sensitivity

Abstract Background: Traditionally, multi-focal breast cancer results in mastectomy. The Alliance Trial offers a paradigm shift in surgical options available for multi-focal breast cancer patients in the context of adjuvant chemotherapy. In the trial, patients with multi-focal disease (&amp;lt; 3 tumors) who underwent breast conservation surgery (BCS) were found to have similar outcomes to patients undergoing mastectomy. BCS for large volume tumors ( &amp;gt;30%) has been cited as having a high potential for cosmetic defect, and hence represents a typical upper limit for potential tissue removal in BCS. Here, we evaluated a patient cohort to better understand the economic impact of the Alliance trial and further categorize patients that would most benefit without suffering cosmetic impact. We employed a novel computational technology to quantify the ratio of tumor size to breast tissue volume. Methods: Using a publicly available, single site cohort (n=243, DUMC) of breast cancer patients that underwent mastectomy, we segmented the tumors using our TumorSight Viz software platform. This platform uses artificial intelligence to segment the tumor and surrounding tissues and allows for a volumetric and morphologic assessment in 3D space. We then applied relevant inclusion/exclusion criteria from the Alliance Trial to the cohort (Saha et al, 2018). In trial eligible patients, we used TumorSight Viz to create a convex hull (CH) around the multi-focal disease using dilations of 1 cm and 2 cm. The volume of the CH, corresponding to proposed surgical extirpation, and the overall breast volume (BV) were then computationally assessed in 3D. The ratio of CH to BV (CH:BV) was calculated and a cutoff of 30% (high potential for cosmetic deformity) was applied. A cost analysis was then carried out. We determined the aggregate per annum savings that could potentially be realized by transforming a subset of mastectomies to BCS by tabulating total costs of mastectomy+reconstruction vs. BCS+WBI (whole-breast irradiation), as well as adjusted for relative rates of adjuvant therapy (~80%) across the nationwide patient population. Results: We found that 19.3% of adjuvant mastectomy patients were eligible for BCS based on Alliance Trial criteria. Of those, 68% had tumor CH:BV &amp;lt; 30% when using a 1 cm dilation around the tumor. When using a 2 cm dilation, 56% had tumor CH:BV &amp;lt; 30%. Together, these results indicate that of all adjuvant mastectomy patients, an estimated 10.8-13.1% are eligible for BCS based on volumetric measures of cosmetically acceptable breast tissue removal. Our economic analysis of BCS vs. mastectomy revealed an estimated $28,500 cost savings for patients with private insurance, suggesting that both decreased costs and improved quality-of-life (QOL) can be mutually aligned. By assessing the nationwide number of patients receiving adjuvant therapy for breast cancer, alongside the percentage potentially eligible for BCS using the above cosmetic defect analysis, we estimate that BCS conversion from mastectomy offers to provide a net savings of $300-350 million annually. Conclusion: The Alliance Trial guidelines unveiled the potential option of BCS in ~20% of patients with multi-focal disease in our cohort, demonstrating considerable cost-savings. Computational tools can further differentiate individuals who may not be best candidates for BCS in this setting, ensuring high QOL and informed decision-making. Citation Format: John Pfeiffer, Matthew Biancalana, Dorys Lopez-Ramos, Bradley Feiger, Anuja Antony. Applying the Alliance Trial Guidelines in Multi-focal Breast Disease Using an Artificial Intelligence Computational Platform: Economic Analysis and Cosmetic Sensitivity [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 PO2-07-04.

Abstract PO1-25-05: Adipose-enriched peri-tumoral stroma prognosticates poorer survival in breast cancers

Abstract Background: Adjuvant breast cancer therapy is informed by whether a tumour is positive or negative for the biomarkers ER, PgR, and HER2, often without regard to level of positivity. Quantitation has been proposed to improve therapeutic management. Adjunctive statistical standardization has been proposed to improve inter-laboratory comparability of biomarkers results. Methods: This primary report utilized adjunctive statistical standardization of machine-quantitated image analysis biomarker assessments. CCTG MA.27 (NCT00066573) is an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER+ and/or PgR+ tumours. IHC ER, PgR, and HER2 were centrally assessed, with FISH (HER2;HER2/CEP17) determinations for equivocal IHC HER2. HSCOREs were statistically standardized to a mean of 0, standard deviation of 1 following Box-Cox variance stabilization transformations of square for ER and natural logarithm for PgR (0.1 was added to 0 HSCOREs). The primary endpoint was STEEP distant disease-free survival (DDFS) at the longest trial follow-up of median 4.1 years. Survival was described with Kaplan-Meier plots. The univariate Wilcoxon (Peto-Prentice) test statistic was used with usual designation of negative/positive (0; &amp;gt;0), and standardized cut-points at standard deviations about mean of 0(&amp;lt;-1; (-1,0]; (0,1]; &amp;gt;1). Cox multivariate regressions adjusted for age, T and N stage, grade, lymphovascular invasion, treatment, and baseline patient demographics, utilized likelihood ratio tests. Nominal significance was p=0.05. Results: Of the 7576 women accrued, 3048 had machine-quantitated image analysis results: 2900 (95%) for ER; 2726 (89%) for PgR. Only 8 women were ASCO/CAP ER- (HSCORE 0); PgR HSCORE was 0 for 533. Statistically standardized units differentiated DDFS ER levels (p&amp;lt; 0.001) and PgR levels (p&amp;lt; 0.001). In adjusted multivariate analyses, higher ER HSCORE was associated with better DDFS (p=0.05) with weak evidence of an association (p=0.11) for standardized HSCORE, and no significant association (respectively, p=0.28, p=0.54) in models with PgR. Higher PgR was associated with better DDFS (p=0.001) in all multivariate assessments, including those with ER. Conclusions: DDFS was superior for patients with higher ER and PgR standardized units compared with those with HSCOREs &amp;lt;-1. Adjunctive statistical standardization, similar to that mandated for clinical practice by the World Health Organization for BMD, should improve inter-laboratory comparability of biomarker results for similar patient populations. Biomarker N DDFS DDFS 5-year (%) 95% CI ER total 2900 ER &amp;lt;-1 506 86 (82, 91) ER (-1, 0] 934 94 (92, 96) ER ( 0, 1] 919 94 (92, 96) ER 1 541 96 (93, 98) PgR total 2726 PgR &amp;lt;-1 734 89 (86, 92) PgR (-1, 0] 439 92 (89, 95) PgR ( 0, 1] 967 95 (93, 96) PgR 1.0 586 98 (97,100) Citation Format: Hannah Lau, Veronique Kiak Mien Tan, Benita Kiat Tee Tan, Yirong Sim, Jelmar Quist, Aye Aye Thike, Puay Hoon Tan, Shazib Pervaiz, Anita Grigoriadis, Kanaga Sabapathy. Adipose-enriched peri-tumoral stroma prognosticates poorer survival in 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 PO1-25-05.

Abstract PO1-27-10: Adjunctive statistical standardization of quantitated machine image analysis of Estrogen and Progesterone Receptors: CCTG MA.27 trial

Abstract Background: Adjuvant breast cancer therapy is informed by whether a tumour is positive or negative for the biomarkers ER, PgR, and HER2, often without regard to level of positivity. Quantitation has been proposed to improve therapeutic management. Adjunctive statistical standardization has been proposed to improve inter-laboratory comparability of biomarkers results. Methods: This primary report utilized adjunctive statistical standardization of machine-quantitated image analysis biomarker assessments. CCTG MA.27 (NCT00066573) is an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER+ and/or PgR+ tumours. IHC ER, PgR, and HER2 were centrally assessed, with FISH (HER2;HER2/CEP17) determinations for equivocal IHC HER2. HSCOREs were statistically standardized to a mean of 0, standard deviation of 1 following Box-Cox variance stabilization transformations of square for ER and natural logarithm for PgR (0.1 was added to 0 HSCOREs). The primary endpoint was STEEP distant disease-free survival (DDFS) at the longest trial follow-up of median 4.1 years. Survival was described with Kaplan-Meier plots. The univariate Wilcoxon (Peto-Prentice) test statistic was used with usual designation of negative/positive (0; &amp;gt;0), and standardized cut-points at standard deviations about mean of 0(&amp;lt;-1; (-1,0]; (0,1]; &amp;gt;1). Cox multivariate regressions adjusted for age, T and N stage, grade, lymphovascular invasion, treatment, and baseline patient demographics, utilized likelihood ratio tests. Nominal significance was p=0.05. Results: Of the 7576 women accrued, 3048 had machine-quantitated image analysis results: 2900 (95%) for ER; 2726 (89%) for PgR. Only 8 women were ASCO/CAP ER- (HSCORE 0); PgR HSCORE was 0 for 533. Statistically standardized units differentiated DDFS ER levels (p&amp;lt; 0.001) and PgR levels (p&amp;lt; 0.001). In adjusted multivariate analyses, higher ER HSCORE was associated with better DDFS (p=0.05) with weak evidence of an association (p=0.11) for standardized HSCORE, and no significant association (respectively, p=0.28, p=0.54) in models with PgR. Higher PgR was associated with better DDFS (p=0.001) in all multivariate assessments, including those with ER. Conclusions: DDFS was superior for patients with higher ER and PgR standardized units compared with those with HSCOREs &amp;lt;-1. Adjunctive statistical standardization, similar to that mandated for clinical practice by the World Health Organization for BMD, should improve inter-laboratory comparability of biomarker results for similar patient populations. Biomarker N DDFS DDFS 5-year (%) 95% CI ER total 2900 ER &amp;lt;-1 506 86 (82, 91) ER (-1, 0] 934 94 (92, 96) ER ( 0, 1] 919 94 (92, 96) ER &amp;gt;1 541 96 (93, 98) PgR total 2726 PgR &amp;lt;-1 734 89 (86, 92) PgR (-1, 0] 439 92 (89, 95) PgR ( 0, 1] 967 95 (93, 96) PgR &amp;gt;1.0 586 98 (97,100) Citation Format: Judy-Anne Chapman, Jane Bayani, Sandip SenGupta, John MS Bartlett, Tammy Piper, Mary Anne Quintayo, Shakeel Virk, Paul Goss, James Ingle, Matthew Ellis, George Sledge Jr, George Budd, Manuela Rabaglio, Rafat Ansari, Richard Tozer, David D'Souza, Haji Chalchal, Silvana Spadafora, Vered Stearns, Edith A. Perez, Karen Gelmon, Timothy Whelan, Catherine Elliott, Lois Shepherd, Bingshu Chen, Karen Taylor. Adjunctive statistical standardization of quantitated machine image analysis of Estrogen and Progesterone Receptors: CCTG MA.27 trial [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 PO1-27-10.

Abstract PO3-01-04: Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort study

Abstract Introduction Neoadjuvant therapy (NAT) is considered the standard of care in patients with HER2-positive breast cancer mainly due to the possibility to adjust the post-neoadjuvant treatment based on the tumor response to NAT. However, there is no convincing evidence on a survival benefit with NAT compared to adjuvant therapy (AT) for HER2-positive breast cancer. The aim of the present study was to compare the two therapeutic strategies in a register-based cohort of Swedish patients with primary operable HER2-positive breast cancer. Method The research database BCBaSe 3.0, which is based on the Swedish National Quality breast cancer register, was used to identify patients with primary operable HER2-positive breast cancer that diagnosed between 2008 and 2020 and received either NAT or AT including chemotherapy and trastuzumab. To mitigate confounding by indication bias, propensity score matching (PSM) with 1:1 matching was applied. The effectiveness of the two therapeutic strategies was investigated through analyzing distant disease-free survival (DDFS), breast-cancer specific survival (BCSS), and overall survival (OS). Multivariate Cox regression analyses were performed for the outcomes of interest to provide Hazard Ratios (HR) and corresponding 95% Confidence Intervals (CI). Results In total, 7258 patients with primary operable HER2-positive breast cancer treated with either NAT or AT were identified, 1789 (24.6%) received NAT and 5469 (75.4%) AT. After 1:1 PSM, 1258 patients in each therapeutic strategy were available for comparisons. After a median follow-up of 63 months, no statistically significant differences between NAT and AT were observed in either outcome (HR for DDFS: 0.97; 95% CI: 0.72 – 1.30; HR for BCSS: 0.69; 95% CI: 0.45 – 1.07; HR for OS: 0.72; 95% CI: 0.50 – 1.05). In subgroup analyses, estrogen-receptor status did not impact the results that remained statistically non-significant between NAT and AT whereas in patients with clinically positive lymph node status, NAT resulted in better BCSS (HR: 0.44; 95% CI: 0.22 – 0.89) and OS (HR: 0.49; 95% CI: 0.29 – 0.90). The latter trend was not evident in patients with clinically negative lymph node status. Conclusion Our study results confirm the equivalence of NAT and AT in terms of prognosis for patients with operable HER2-positive disease and imply a potential benefit of NAT compared to AT in patients with clinically positive lymph node status. Considering the emerging treatment strategies in HER2-positive breast cancer patients treated with NAT (pertuzumab as a part of NAT, T-DM1 as post-neoadjuvant therapy) that have been shown to improve survival but are not reflected in the study cohort, NAT should be considered as the strategy with the higher possibility to improve long-term prognosis for patients with HER2-positive disease. Citation Format: Servah Hosseini-Mellner, Åsa Wickberg, Antonis Valachis, Andreas Karakatsanis. Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort 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 PO3-01-04.