Sardesai, Sagar

PURPOSE EA1181 (ClinicalTrials.gov identifier: NCT04266249 ) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)–positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point—3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)—will be reported when data mature. METHODS Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER–]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER– and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER– tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER– and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

603 Background: Accurate prediction of pathologic complete response (pCR) after preoperative therapy for HER2-positive (HER2+) breast cancer can help triage patients to immediate surgery vs additional preoperative therapy. Pre-surgery (i.e., after neoadjuvant therapy) imaging studies may help estimate the likelihood of pCR. In EA1181, patients (pts) with stage II-IIIA HER2+ breast cancer received four cycles of preoperative taxane, trastuzumab, and pertuzumab (THP×4). Pre-surgery imaging was required, though the specific imaging modality was not mandated. Here, we report the accuracy of pre-surgery breast MRI to predict pCR (ypT0/Tis, ypN0). Methods: Among 2,141 pts treated with THPx4, 1,378 had pre-surgery breast MRI and were representative of the overall cohort, although T3 tumors were more common (16% vs 9%). MRI reports were available for 1,351 pts; all reports were centrally reviewed and classified as radiologic complete response (rCR; no residual tumor enhancement and normalization of lymph nodes, if applicable) or radiologic residual disease (rRD). Reports with indeterminate radiologic response were independently reviewed by two study radiologists blinded to pathology outcomes. Among pts with rCR who had pathologic residual disease (pRD), we also assessed the extent of residual disease by residual cancer burden (RCB) score. Among pts with rRD who had a pCR, we determined the proportion who only had residual ductal carcinoma in situ (DCIS). Results: See Table. Conclusions: After neoadjuvant therapy, preoperative MRI accurately predicted pCR in 86% of patients with HER2+/ER− disease and may help identify patients who can proceed directly to surgery. MRI is insufficient to predict pCR for pts with HER2+/ER+ disease, as only 55% with complete response on MRI had a pCR at surgery. A pre-surgery MRI that indicated residual disease was accurate in 80% of pts with HER2+/ER+ disease, but in only 45% of pts with HER2+/ER- cancer. Accurately predicting residual disease after THPx4 allows for consideration of additional therapy that may increase the chance of pCR. Combining imaging like MRI with other biomarkers, such as tissue-based markers or circulating tumor DNA, may improve prediction of pCR and facilitate personalization of treatment decisions in HER2+ breast cancer. All pts with pre-surgery MRI (n=1351)pCR rate overall in this cohort = 47% MRI result Pathology pCR pRD rCR 70.6% (341/483) 29.4%(142/483) 78% had RCB1 rRD 34%(295/868) 21% of 295 had DCIS only 66.01% (573/868) ER- (n=589)*Overall pCR rate in ER- subset = 68% MRI result Pathology pCR pRD rCR 86.1% (205/238) 13.9% (33/238) 85% had RCB1 rRD 55.3% (194/351) 19% of 194 had only DCIS 44.7% (157/351) ER+ (n= 762)*Overall pCR rate in ER+ subset = 31% MRI result Pathology pCR pRD rCR 55.5% (136/245) 44.5% (109/245) 76% had RCB1 rRD 19.5% (101/517) 26% of 101 had only DCIS 80.5% (416/517)

Abstract Background: The association of TILs with pathologic complete response (pCR) and survival in HER2+ breast cancer is not well established with several prior studies showing inconsistent results. In this secondary analysis of EA1181, we evaluated the association between stromal TILs (sTILs) and pCR rates. Methods: EA1181 (NCT04266249) enrolled patients (pts) with anatomic clinical stage II/III HER2+ breast cancer who preoperatively received 4 cycles of trastuzumab and pertuzumab with 12 weeks of paclitaxel or docetaxel q3w x 4 (THP), followed by surgery. sTILs density was assessed on full-face hematoxylin and eosin (H&E)-stained tumor biopsy sections. sTILs scores were analyzed per protocol as a continuous variable (every 10% increment) and as a categorical variable (<10% vs 10-60% vs >60% as per Denkert et al, 2018), and also with an exploratory 30% cutoff commonly used in TNBC. Cox proportional hazards models were used to examine the association between sTILs and pCR, adjusting for available baseline factors. The associations between sTILs (by category) and clinicopathologic characteristics were examined using Fishers’ exact test. Results: Among 2141 pts with HER2+ BC treated on EA1181, H&E slides were available for 1328 (62%). The study population evaluated for sTILs was comparable to the overall population. pCR rates were 44.5% overall, 64% for HER2+/ER- and 33% for HER2+/ER+ disease. sTILs distribution was: 623 (47%) <10%, 698 (52%) 10-60%, and 7 (0.5%) >60%, which led us to merge the latter two groups (705 [53%] had ≥10% sTILs). In univariable and multivariable analyses, increasing sTILs (as a continuous variable) were associated with increasing pCR rates in both HER2+/ER+ and HER2+/ER- disease (p<0.001; Table). sTILs analyzed as a categorical variable (<10% vs ≥10%) were significantly associated with pCR for all patients (combined) and for those with HER2+/ER+ disease. In exploratory analysis using a cutoff of <30% vs ≥30% sTILs, an association with pCR was also seen in univariable analysis for both HER2+/ER+ disease (p<0.001) and HER2+/ER- disease (p=0.045), though in multivariable analysis with clinical factors, sTILs >30% remained a significant predictor for pCR only in HER2+/ER+ disease. Additional exploratory analysis with other molecular biomarkers, intrinsic subtypes, and immune signatures will be presented. Conclusion: sTILs were associated with pCR after THP, further supporting the important role of immune mechanisms in HER2+ breast cancer, and highlighting a potentially robust predictive tool to assess pathologic response. Baseline sTILs could potentially inform the preoperative design of future trials of therapy optimalization. Association of baseline sTILs with recurrence free survival in EA1181 will be reported in the future. Citation Format: S. S. Badve, F. Zhao, N. Tung, Y. Gokmen-Polar, C. C. O'Sullivan, A. Prat, E. P. Winer, J. L. Wright, A. Recht, A. C. Weiss, J. A. Tjoe, S. M. Feldman, G. B. Rocque, M. Smith, N. Unni, S. Sardesai, S. Tang, S. Modi, W. J. Irvin, P. Villagrassa, C. Battelli, A. K. Krie, N. Bagegni, M. A. George, M. L. Telli, V. F. Borges, N. D’Abreo, P. Shah, K. D. Miller, A. H. Partridge, L. A. Carey, A. M. DeMichele, A. C. Wolff, ECOG-ACRIN.Tumor infiltrating lymphocytes (TILs) and pathologic complete response (pCR) in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): secondary results from the ECOG-ACRIN EA1181/CompassHER2 pCR trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS1-04.

501 Background: EA1181 (NCT04266249) is a single-arm trial of neoadjuvant THP for patients with clinical anatomic stage II/III HER2+ breast cancer; patients with cT4 or cN3 disease were excluded . Assessing the primary endpoint, 3-year recurrence-free survival in patients with a pCR (ypT0/Tis, ypN0), requires longer follow-up. Here, we present results for the secondary objective of pCR rate and its relation to clinicopathologic factors and the HER2DX pCR likelihood score (Reveal Genomics) derived from gene expression and clinical features. Methods: Patients received 4 cycles of trastuzumab and pertuzumab (HP) with weekly paclitaxel (12 weeks) or docetaxel (q3w x 4), followed by surgery. Clinicopathologic features were assessed for all patients and HER2DX pCR score (stratified by ER status) was determined using the diagnostic biopsy in a representative subset of study participants. Results: 2175 patients were enrolled. Median age was 55 years (range 22-88 years); 58% had clinical stage IIA, 33% stage IIB, and 9% stage III. 45% had nodal involvement (mostly cN1). 781 tumors were HER2+/ER- and 1394 HER2+/ER+ (locally tested ). 2141 patients started THP, for whom the pCR rate was 44% overall, 63.7% in HER2+/ER- and 32.4% in HER2+/ER+ tumors. Disease progressed during THP in 16 patients (0.7%). The pCR rate varied inversely to the proportion of cells staining for ER among patients with HER2+/ER+ breast cancer: 1-10%+, 62.5%; 11-69%, 51.6%; ≥70%, 22.5% (p <0.001). The pCR rate was significantly associated with higher grade, especially in HER2+/ER+ disease. T and N stage did not significantly affect pCR rate. Among 569 patients assessed for the HER2DX pCR score, the pCR rate was significantly greater for patients with a higher vs lower score, regardless of ER status (Table). Further correlations and interactions will be presented. Conclusions: Neoadjuvant THP resulted in pCR in nearly two-thirds of pts with clinical stage II/III HER2+/ER- and in one-third with HER2+/ER+ breast cancer. There was no association with clinical stage. Lower ER expression and higher grade were associated with higher pCR rates. The HER2DX pCR score was a significant predictor of pCR, regardless of ER status. Clinical trial information: NCT04266249 . All Participants HER2+/ER- HER2+/ER+ # patients enrolled pCR rate (95% CI) # patients enrolled pCR rate (95% CI) # patients enrolled pCR rate (95% CI) Evaluable Cohort 2141 44%(42-46%) 774 64%(60-67%) 1367 32%(30-35%) HER2DX Cohort 569 48%(44- 52%) 230 69% (63-75%) 339 34%(29-39%) HER2DX pCR-high score 182 (32%) 68%(60-74%) 147 (64%) 70% (62-77%) 36 (11%) 58%(41-74%) HER2DX pCR-medium score 161 (28%) 67% (59- 74%) 70 (30%) 74%(62- 84%) 89 (26%) 61%(50-71%) HER2DX pCR-low score 226 (40%) 19%(14- 25%) 13 (6%) 31%(9-61%) 214 (63%) 18%(13-24%) P-value HER2DX score <0.001 0.010 <0.001

Abstract Background: Despite evidence of substantial breast cancer risk reduction, few high-risk women adopt chemopreventive medications such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Women with benign breast disease, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have an increased risk of developing breast cancer and derive a greater benefit from antiestrogens compared to other high-risk women. Reasons for low uptake of chemoprevention include insufficient patient and clinician knowledge about antiestrogens, time constraints during the clinical encounter, and concerns about side effects. To address these barriers, we have developed patient and provider web-based decision support tools to improve informed choice about breast cancer chemoprevention among women with AH or LCIS. Study design: We are conducting a cluster-randomized controlled trial of clinical decision support to improve chemoprevention informed choice among women with AH or LCIS and their treating providers. Twenty-six U.S. sites through the SWOG Cancer Research Network were randomly assigned 1:1 to standard educational materials alone or in combination with the patient-centered decision aid (RealRisks) and provider decision support tool (BNAV). A total of 415 patients and 200 healthcare providers will be recruited from these sites. RealRisks consists of interactive modules to calculate personalized breast cancer risk and elicit preferences on chemoprevention. The modules are available in English and Spanish. BNAV is comprised of self-directed case-based learning modules on breast cancer risk assessment and chemoprevention. Patients complete questionnaires at baseline, 6 and 12 months. Providers complete surveys at baseline and after their enrolled patient’s 6-month clinical encounter. The primary endpoint is chemoprevention informed choice at 6 months, using a measure combining knowledge, attitude, and intention scales. Secondary endpoints include perceived breast cancer risk/worry, chemoprevention knowledge/intention, decision conflict/regret, shared decision-making, and chemoprevention uptake. For patients who begin chemoprevention, adherence and reasons for discontinuation are assessed annually for up to 5 years. Barriers and facilitators to implementing RealRisks and BNAV into clinic workflow will be assessed by conducting patient and provider interviews at baseline and mid-implementation. Eligibility criteria: Eligible patients include women, age 35-74 years, with AH or LCIS, no history of breast cancer, no prior use of SERMs or AIs, no bilateral mastectomies, English or Spanish-speaking, and access to the internet. Eligible providers include breast surgeons, medical oncologists, primary care providers, and physician extenders who see patients with AH or LCIS. Statistical methods: We have 90% power to detect a 15% increase in the frequency of chemoprevention informed choice with a 1-sided 0.025 level test, assuming an intraclass correlation (ICC) of 0.02 to account for clustering, roughly equal accrual at each site, 10% loss to follow-up, and ≤10% event rate in the control arm. Current/target accrual: The trial was activated on 9/1/2020. As of 7/7/2022, all 26 sites have been randomized, 157/200 providers and 184/415 patients have been enrolled. Discussion: Our hybrid effectiveness/implementation study seeks to evaluate the effectiveness of a multi-level intervention in promoting informed decision-making about breast cancer chemoprevention. Study results will provide valuable insights on how the decision support tools are integrated in diverse clinical settings. Citation Format: Katherine D. Crew, Garnet Anderson, Kathryn Arnold, Andrew Stieb, Jacquelyn N. Amenta, Cynthia Law, Ana Sandoval-Leon, Sarah Colonna, Tari King, Debra Mangino, Sandhya Pruthi, Maria Grosse Perdekamp, Christa Braun-Inglis, Stacy Krisher, Lisa Yee, Danielle Bertoni, Samantha Seaward, Kari B. Wisinski, Justin Floyd, Corrine Zarwan, Tarah J. Ballinger, Lindi VanderWalde, Masey M. Ross, Preston Steen, Shelly Lo, Alison Conlin, Kathleen Yost, John Ellerton, Erin Lin, Holly J. Pederson, Sagar Sardesai, Cheryl Jernigan, Dawn Hershman, Marian L. Neuhouser, Banu K. Arun, Rita Kukafka. SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-15-01.

(1) Background: The objective of this study was to determine the long-term efficacy of fractional CO2 laser therapy in breast cancer survivors. (2) Methods: This was a single-arm study of breast cancer survivors. Participants received three treatments of fractional CO2 laser therapy and returned for a 4 week follow-up. Participants were contacted for follow-up at annual intervals. The Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Female Sexual Distress Scare Revised (FSDS-R), the Urinary Distress Inventory (UDI), and adverse events were collected and reported for the two-year follow-up. The changes in scores were compared between the four-week and two-year and the one-year and two-year follow-ups using paired t-tests. (3) Results: In total, 67 BC survivors were enrolled, 59 completed treatments and the four week follow-up, 39 participated in the one-year follow-up, and 33 participated in the two-year follow-up. After initial improvement in the VAS from baseline to the four week follow-up, there was no statistically significant difference in the VAS score (mean Δ 0.23; 95% CI [−0.05, 0.51], p = 0.150) between the four week follow-up and the two-year follow-up. At the two-year follow-up, the FSFI and FSDS-R scores remained improved from baseline and there was no statistically significant change in the FSFI score (mean Δ −0.83; 95% CI [−3.07, 2.38] p = 0.794) or the FSDS-R score (mean Δ −2.85; 95% CI [−1.88, 7.59] p = 0.227) from the one to two-year follow-up. The UDI scores approached baseline at the two-year follow-up; however, the change between the one- and two-year follow-ups was not statistically significant (mean Δ 4.76; 95% CI [−1.89, 11.41], p = 0.15). (4) Conclusions: Breast cancer survivors treated with fractional CO2 laser therapy have sustained improvement in sexual function two years after treatment completion, suggesting potential long-term benefit.

e18739 Background: Hair loss is a well-known side effect of chemotherapy. The Paxman Hair Loss Prevention System, a scalp cooling device, has been shown to be effective in reducing chemotherapy induced alopecia in patients receiving chemotherapy (Nangia, JAMA, 2017). The National Comprehensive Cancer Network and the European Society for Medical Oncology guidelines have recommended scalp cooling as category 2A and 2B options, respectively. Methods: The real world use of scalp cooling using the Paxman device, as documented by orders through the Paxman Hub during the years of 2017-2020 was summarized. Descriptive statistics were used to summarize demographics and utilization. Results: Data from 6649 patients who used scalp cooling were reviewed. Patients with breast cancer were the most common users of scalp cooling (78%, n=5197) followed by gynecology (12%, n=775), gastrointestinal (3%, n=201), lung (1%, n=81) and genitourinary (1%, n=52). The majority of patients were between the ages of 45-65 (55%), followed by 65-74 (18%), older than 75 (5%), and 25-44 (2%). Average number (#) of cycles of cooling completed was 6.53 (range of average # of cycles 4.50-12). Scalp cooling with this device was commonly used in 39 out of 50 states. Conclusions: This is the largest report of scalp cooling usage in the real world setting in the USA, including scalp cooling usage in older adults. Uptake of scalp cooling across various cancers has not been uniform and this deserves further study.

Abstract Objective: The objective of this pilot study was to evaluate the change in sexual function following treatment with fractional CO2 laser therapy in breast cancer (BC) survivors with genitourinary syndrome of menopause (GSM). Methods: A single-arm feasibility study of BC survivors with symptoms of GSM, including dyspareunia and/or vaginal dryness, was conducted. Participants who received three treatments with fractional CO2 laser and 4-week follow-up were contacted for patient-reported outcomes and adverse events at 12 months. Sexual function was measured using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale Revised (FSDS-R). Descriptive statistics were calculated for patient demographics and disease characteristics for the set of participants who agreed to long-term follow-up and those who were lost to follow-up. FSFI and FSDS-R scores were summarized at baseline, 4 weeks and 12 months, as well as the change from baseline, and were compared using a Wilcoxon signed rank test. Results: A total of 67 BC survivors enrolled, 59 completed treatments and 4-week follow-up; 39 participated in the 12 month follow-up. The overall FSFI score improved from baseline to 4-week follow-up (median Δ 8.8 [Q1, Q3] (QS) (2.2, 16.7)], P < 0.001). There were improvements at 4 weeks in all domains of the FSFI (P < 0.001 for each) including desire (median Δ 1.2; QS [0.6, 1.8]), arousal (median Δ 1.2; QS [0.3, 2.7]), lubrication (median Δ 1.8 (0, 3.3), orgasm (median Δ 1.2; QS [0, 3.6]), satisfaction (median Δ 1.6 (0.4, 3.2)), and pain (median Δ 1.6 (0, 3.6). The FSDS-R score also improved from baseline to 4-week follow-up (median Δ −10.0; QS [−16, −5] P < 0.001) indicating less sexually related distress. The scores of the FSFI and FSDS-R remained improved at 12 months and there were no serious adverse events reported. Conclusions: In BC survivors with GSM, the total and individual domain scores of the FSFI and the FSDS-R improved after fractional CO2 laser therapy. Video Summary: http://links.lww.com/MENO/A711.

202 Background: Fractional CO2 laser therapy is an emerging treatment for GSM. The objective of this study was to determine the feasibility, tolerability and preliminary efficacy of fractional CO2 laser therapy in BC survivors. Methods: This was a single arm feasibility study of BC survivors with dyspareunia and/or vaginal dryness. Participants received three treatments with office-based fractional CO2 laser on at least 30 day intervals and returned for a one-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in a minimum of 80% of patients. Primary efficacy was evaluated using the mean change (∆) in the score on the Vaginal Assessment Scale (VAS). Secondary efficacy endpoints included mean ∆ in scores on the Female Sexual Function Index (FSFI) and Urogenital Distress Inventory (UDI). Descriptive statistics (means and 95% confidence intervals (CI) for continuous variables and proportions for categorical variables) were used. Results: The study is ongoing with 65 patients enrolled. To date, 37 patients have completed all study treatments and follow-up. Median age for those who have completed treatment was 57 years (range 34-72). Most were ER/PR positive (78%) and Her 2 negative (81%) with stage I (43%) or II (41%) BC. Ninety-five percent were receiving endocrine therapy, most commonly aromatase inhibitors (73%). No SAEs were reported in the 37 patients who have completed study treatments and their outcomes are as follows. Based on the VAS, 78% reported moderate-severe dyspareunia and 89% reported moderate-severe vaginal dryness at baseline. At follow up, 28% reported moderate-severe dyspareunia and 28% reported moderate-severe vaginal dryness. The VAS score improved from baseline to follow up (mean ∆ 4.1; 95% CI [3.1, 5.1]). Similarly, the FSFI score improved (mean ∆ -10.0; 95% CI [-13.2, -6.9]) and the UDI score improved (mean ∆ -5.7; 95% CI [-10.1, -1.3]). Final efficacy analysis will be reported once all patients have completed all time points. Conclusions: Fractional CO2 laser treatment is feasible and tolerable in BC survivors and may reduce symptom burden from GSM. A randomized controlled trial with sham laser is currently in development. Clinical trial information: NCT03307044.