Introduction: Axillary dissection is currently recommended for more than two positive nodes or for any positive nodes after neoadjuvant chemotherapy. However, the value of axillary dissection is uncertain. Enthusiasm for neoadjuvant chemotherapy (NAC) in early-stage breast cancer has intensified. It is possible that more liberal use of neoadjuvant chemotherapy will lead to an increase in recommendations for axillary dissection. Here, we compared the rate of ALND candidacy in early-stage breast cancers between those who received NAC and adjuvant chemotherapy (AC). Method: After Institutional Review Board (IRB) approval, we performed a retrospective analysis of the National Cancer Database (NCDB). We identified cN0, cT1-2, M0, stage I, and II female breast cancers who had primary site surgery and received chemotherapy between 2010-2021. Patients with a history of another malignancy, no axillary surgery, unknown clinical or pathologic nodal status, an unknown number of positive nodes, and a previous history of neoadjuvant radiotherapy or endocrine therapy were excluded. ALND candidacy was considered positive in the NAC group if any positive nodes were recorded, and it was considered positive in the AC group if more than two positive lymph nodes were documented after axillary surgery. Patient and tumor characteristics were compared across those who received NAC and AC. Multivariable logistic regression was used to determine variables associated with ALND candidacy. Patients were categorized into four phenotypes: 1- hormone receptor-positive (HR+) and HER2+ as triple positive (TP); 2- HR+ and HER2- as hormone-positive (HR+); 3- Hormone receptor-negative (HR-) and HER2+ as HER2+; and 4- HR- and HER2- as triple negative (TN). Considering different rates of pathologic response to NAC, we performed a subgroup analysis by phenotype to compare the ALND candidacy amongst those who got NAC and AC stratified by the stage of the disease. Analysis was performed using Stata software, version 18. Results: A total of 295,110 cases were selected. The mean age of the patients was 56.6+/-12.0 years; 79.3% were White, invasive ductal carcinoma (IDC) constituted 83.6%, and 41.5% underwent mastectomy. The mean number of removed and positive nodes were 5.4 and 0.9, respectively. NAC was administered in 38,315 (13%) of the patients, and 9.6% of them had positive nodes and were ALND candidates, while 25,017/256,795 (9.7%) of the AC group had more than two positive nodes and were considered ALND candidates (p=0.24). We performed a subgroup analysis by phenotype. TN breast cancers constituted 81,924 patients. Of them, 71.6% received AC, and 28.4% received NAC. The prevalence of ALND candidacy was 3% in the AC and 5.9% in the NAC group (p<0.001). HR+ patients included 160,304 patients, of whom 95.6% received AC and 4.4 % received NAC. Among HR+ patients, 13.2% of the AC group and 23.7% of the NAC group were ALND candidates (p<0.001). TP breast cancers included 22,708 cases, where 89% received AC and 11% received NAC. ALND candidacy was also higher in the NAC group compared to the AC group among TP breast cancers (11.2 % to 6.5%, respectively, p<0.001). The HER2+ phenotype included 20,566 cases. In the HER2+ group, ALND candidacy in the NAC group compared to the AC group did not increase, and a decline in the ALND candidacy after NAC was observed (5.0% to 6.1%), p=0.008. This decline was not statistically significant in stage 1 HER2+ cases, but it was statistically significant in stage 2 HER2+ cases (5.1% to 8.9%) (p<0.001). On multivariable logistic regression model adjusted for age, Charlson Comorbidity score, clinical tumor stage, grade, HR status, HER2 status, lymphovascular invasion, type of primary site surgery (mastectomy or lumpectomy), and the year of diagnosis, NAC increased the rate of ALND candidacy compared to AC (OR:2.03, 95%CI 1.9-2.1; p<0.001). Conclusion: Increasing the use of NAC in early-stage breast cancer is likely to increase the recommendation for axillary dissection, especially for HR+ tumors, which are less likely to respond. Therefore, the timing of chemotherapy utilization in early-stage breast cancers should be cautiously considered. Citation Format: Mahtab Vasigh, Fabian Johnston, Fasika Molla Abreha, Taleaa Masroor, David Farhat, Lisa Jacobs, David Euhus, Olutayo Sogunro. The Impact of the Neoadjuvant Chemotherapy Compared to Adjuvant Chemotherapy in ALND Candidacy in cN0, cT1,2 early-stage Breast Cancer, A National Cancer Database Analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-08-01.

512 Background: Conjugated estrogen/bazedoxifene (CE/BZA), the first tissue selective estrogen complex, was developed as an alternative to combination estrogen and progesterone therapy to treat hot flashes and osteoporosis. Preclinical studies found that CE/BZA reduced mammary ductal proliferation and increased expression of anti-tumorigenic markers in breast stroma. Our study aimed to determine if a pre-surgical window-of-opportunity intervention with CE/BZA in women with ductal carcinoma in situ (DCIS) had a protective effect on the duct epithelium and stroma of DCIS lesions without impacting quality of life. Differences between CE/BZA and placebo arms for the primary endpoint, change in Ki-67 protein expression, and quality-of-life endpoints are reported here. Methods: This multicenter, randomized, double-blind placebo-controlled Phase 2 trial was conducted between 9/19/17 and 8/21/24. Postmenopausal women with estrogen receptor positive (ER+) DCIS undergoing surgery were randomized to CE 0.45 mg /BZA 20 mg or placebo for 28 +/-7 days. Percentage of nuclei staining for Ki-67 was evaluated on slides from the baseline core biopsy and surgical specimen. Changes were compared between arms using the two-sample t-test, while changes within arms were analyzed using paired t-test. Analyses were done on log2 scale to satisfy the normality assumption. The Breast Cancer Prevention Trial Eight Symptom Scale (BESS) and Menopause-Specific Quality of Life (MENQOL) surveys were self-administered by patients before and after the intervention. Wilcoxon’s signed-rank and rank-sum tests were used to perform within- and between-arm comparisons, respectively. Results: Of the 171 patients consented,141 enrolled, and 117 completed the study. Ninety-four patients (46= CE/BZA, 48=placebo) took >80% of the medication and had Ki-67 evaluated at baseline and post-intervention. The BESS and MENQOL surveys were completed by 100 and 108 patients, and 125 patients were evaluated for toxicity. The mean absolute change in Ki-67 was -5.62 (SD=10.2; p=0.003) in the CE/BZA arm and -1.07 (SD=10.8; p=0.6) in the placebo arm, with a greater reduction in CE/BZA arm (p=0.016). There was no difference between arms in the BESS score across all 8 domains or in the MENQOL score. However, within each arm, vasomotor symptoms decreased in the CE/BZA arm (p=0.002) but not in the placebo arm (p=0.4). No grade > 3 treatment related adverse events were reported. Conclusions: In this prospective randomized clinical trial, CE/BZA significantly reduced epithelial proliferation in ER+ DCIS with no impact on quality of life compared to placebo. These results support consideration that CE/BZA is a safe option to manage menopausal symptoms for women concerned about their risk of developing breast cancer, and provide supportive evidence that CE/BZA may reduce the risk of developing invasive breast cancer. Clinical trial information: NCT02694809 .

Background The most optimal surgical strategy for ipsilateral isolated axillary recurrence (AR) in breast cancer is unknown. Axillary lymph node dissection (ALND) has historically been implemented; however, there may be an evolving role for targeted axillary dissection (TAD). Methods A retrospective analysis was conducted on patients with invasive breast cancer, followed by AR. Clinical and operative strategies were collected, with primary endpoints including overall survival (OS) and progression-free survival (PFS). Results In total, 21 (10.2%) patients were identified with AR. Of this subset of patients, 15 (71.4%) underwent ALND, and six (28.6%) underwent TAD. Univariable and multivariable analyses did not observe a significant association between TAD versus ALND at the time of recurrence with PFS. Univariable analysis demonstrated a significant association between adjuvant radiation and endocrine therapy at first recurrence and PFS benefit. Conclusions Following AR, no PFS benefit was observed between those managed with TAD versus ALND, which highlights an additional area of consideration for possible axillary de-escalation.

Kaplan-Meier survival plot of pCR vs. non-pCR in both trebananib and control arms

RPPA endpoints and genes/signatures involved in TIE2 signaling that were studied

Representativeness of Study Participants

As indications for hereditary cancer genetic testing (GT) for patients with breast cancer (BC) expand, breast surgery teams offer GT to newly diagnosed patients to inform surgical plans. There is, however, limited data on the experiences of patients undergoing cancer GT by non-genetic providers. This study used in-depth interviews with 21 women recently diagnosed with BC at a large academic health system to capture their experiences. Post-positivist codebook thematic analysis was used to identify major themes from the interviews. Participants reported an overall positive experience of this GT process, stating that they prefer GT at an existing appointment shortly after their diagnosis, even though they described the conversation as brief. Many participants indicated thinking about or desiring GT before the offer was made. Interestingly, most participants did not see surgical decision-making as the main reason for GT and were instead motivated by concern for relatives and to have complete information. Interview data indicated areas for improvement in patient-provider communication, and most participants agreed that additional reference information on GT in the form of written or video materials would be helpful. Offering GT at an initial breast surgery appointment is acceptable and desired by patients with a new BC diagnosis and should be considered as a way to increase access to GT for these patients. However, additional information for patients is needed to close gaps in communication and provide a trustworthy reference following a busy medical appointment.

Breast-conserving surgery is often discouraged in BRCA gene carriers with early onset breast cancer. The genetic variant carrier breast cancers are more likely to be multifocal or multicentric (MFMC). This retrospective study includes newly diagnosed patients with breast cancer undergoing genetic testing between 2010 and 2021 within the Johns Hopkins Regional Health System. After excluding patients who received neoadjuvant chemotherapy or stage IV breast cancers, patients were divided into two groups: those who tested positive for a variant recognized by the National Comprehensive Cancer Network as predisposing the patient to breast cancer (ATM, BRCA1, BRCA2, CHEK2, NF1, PALB2, RAD51C, RAD51D, and TP53) and those who tested negative. Pathologic features of the tumors were compared, focusing on evidence for MFMC disease, defined as more than one malignant foci more than 5 mm apart. Among the 282 eligible cases, 69 (24

Trebananib vs Control pCR–Biomarker Associations

Using Contemporary Controls and Adjusting for Time Trends in I-SPY2: The Time Machine

PDF file - 67K, Genes modulated by tamoxifen but not placebo in an analysis that combined pre- and post-menopausal women.

Supplementary Table 1 from Identification of Breast Cancer DNA Methylation Markers Optimized for Fine-Needle Aspiration Samples

Supplementary Table 2 from Identification of Breast Cancer DNA Methylation Markers Optimized for Fine-Needle Aspiration Samples

PDF file - 3706K, Pathway Analysis.

PDF file - 37K, Detailed RT-PCR results.

PDF file - 42K, RT-PCR primer sequences.

Supplementary Figure 1 from <i>RASSF1A</i> Polymorphism A133S Is Associated with Early Onset Breast Cancer in <i>BRCA1/2</i> Mutation Carriers