Use Of Neoadjuvant Endocrine Therapy Research Articles

Abstract PO1-17-10: Impact of COVID19 on neoadjuvant endocrine therapy use in breast cancer: A National Cancer Database analysis

Abstract Background: Neoadjuvant endocrine therapy (NET) is associated with similar response rates as neoadjuvant chemotherapy in hormone receptor positive (HR+) breast cancer (BC), with less toxicity. While gene expression assays such as the 21-gene recurrence score (RS) have led to decreased chemotherapy use in early HR+/HER2- BC, NET is often underutilized. In 2020, the COVID19 pandemic led to disruption in oncologic care, including cancellation of surgeries. Guidelines for BC management during the pandemic recommended NET for HR+/HER2- BC patients unable to obtain surgery due to pandemic restrictions. We evaluated NET use in 2020, compared to NET use in prior years. Methods: Female pts with nonmetastatic HR+/HER2- BC diagnosed between 2016 and 2020 were identified from the 2004-2020 National Cancer Database (NCDB). Annual number of pts receiving NET, and duration of use, were compared between years, and characteristics of pts treated with and without NET were evaluated within and across years, using Chi-squared test for categorical variables and Wilcoxon rank-sum test or Kruskal-Wallis test for continuous variables. Results: 554,733 pts met inclusion criteria; 84.50% white, 9.19% Black, 4.06% Asian; 5.88% Hispanic. 25,553 (4.61%) pts received NET. Annual NET use increased slightly between 2016 and 2018 [3.25% vs 3.49% (p=0.021) vs 3.89% (p < 0.0001)], remained stable in 2019 (3.98%), and then increased to 8.67% in 2020 (p < 0.0001). Median duration of NET remained relatively stable between 2016 and 2019 [74 days (d), 68d, 73d and 61d, 2016-2019] but declined in 2020 (56d, p< 0.0001 for 2020 vs 2016, 2017, 2018, and 2019). Older age and greater comorbidities were associated with NET use in all years (p < 0.0001). No racial association with NET use was seen in 2016-2018, but Black race was associated with greater NET use in 2019 (p=0.0122) and 2020 (p < 0.0001). Lobular histology, moderate grade, larger tumor size, and node involvement were associated with increased NET use in all years (p < 0.0001). Progesterone receptor positivity (PR+) and lower Ki67 were associated with NET use in 2020 (p=0.0007 and p< 0.0001), but not prior. Median tumor size for pts receiving NET was smaller in 2020 (16mm) compared with prior years (22, 23, 22, and 21mm for 2016-2019, p< 0.0001). Annual RS use increased for all pts between 2016 (34.59%) and 2020 (43.47%). RS use in NET pts was stable in 2016 (27.79%) and 2017 (27.54%), with modest increase in 2018 (29.56%; p 0.094, 2016 vs 2018, p=0.045, 2017 vs 2018), and then increased annually in 2019 (33.28%, p=0.0001) and 2020 (40.64%, p< 0.0001). Median RS was higher in pts receiving NET than in pts who did not in 2016-2019 (p=0.0078, 0.0003, 0.0271, and < 0.0001), but was similar in 2020 (RS=16; IQR 11, 22). Conclusions: Frequency of NET administration more than doubled in 2020, but duration was shorter than in prior years, possibly due to use of NET as “bridging therapy” due to COVID19 restrictions. Black race was associated with receipt of NET in 2020, possibly reflecting disparate impact of COVID19 on Black communities. NET use in 2020 was also associated with smaller tumor size, lower Ki67, and greater likelihood of PR+ disease than in prior years. Use of RS to guide NET increased annually, beginning in 2018. Association of NET with older age, greater comorbidities, higher stage, moderate grade, and lobular histology were seen in all years. Citation Format: Della Makower, Jaeun Choi, Susan Fineberg. Impact of COVID19 on neoadjuvant endocrine therapy use in breast cancer: A National Cancer Database analysis [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 PO1-17-10.

Abstract PO3-23-02: Delays in breast cancer surgery during the COVID-19 pandemic: A population-based analysis

Abstract BACKGROUND: At various times during the COVID-19 pandemic, access to operating room resources were restricted in Ontario, Canada. This resulted in triaging of all non-urgent cases, including breast cancer (BC) surgery. Recent single institution studies have identified treatment delays during the immediate pandemic time period. The objective of this study was to assess the impact of the pandemic on wait times for breast cancer surgery at a population level. METHODS: We identified patients with a BC diagnosis between January 1, 2018 and November 30, 2021 in Ontario, Canada. Three cohorts were defined based on the following time periods: pre-pandemic (baseline) (January 2018 to 14 March 2020), immediate pandemic (March 15, 2020 to June 13, 2020), and peri-pandemic (June 14, 2020 to November 30, 2021). Time to event analysis was conducted for time to a patient’s first BC surgery. A subgroup analysis was conducted for patients who underwent neoadjuvant chemotherapy (NAC). RESULTS: The study cohort consisted of 36,639 patients with a new diagnosis of BC. Of them 30,862 patients underwent surgery (84.2%) within 18 months after diagnosis. The probability of BC patients undergoing surgery each month from their date of diagnosis was significantly lower (i.e. longer wait times) for patients diagnosed in the immediate and peri-pandemic period compared to patients diagnosed in the pre-pandemic period (log-rank P < 0.001). At eight weeks from date of diagnosis, the probability of having had surgery was 65.1% (95% CI: 64.5-65.8%) for patients diagnosed in the pre-pandemic period, 56.1% (95% CI: 53.6-58.6%) for immediate pandemic and 59.0% (95% CI: 58.2-59.8%) for peri-pandemic. Time for 80% of patients to have BC surgery was 5.4 months in the pre-pandemic, 5.9 months in the immediate pandemic, and 6.0 months in the peri-pandemic period. Among patients who received NAC (N=6,121; 16.7% of cohort), the probability of undergoing surgery in each month from the date of diagnosis was similar for patients diagnosed in the pre and peri-pandemic periods, but was higher (i.e. shorter wait time) for the cohort of patients diagnosed during the immediate pandemic time period (log-rank P < 0.001). At six months from date of diagnosis, the probability of surgery for patients who received NAC was 50.7% (95% CI: 48.9-52.5%), 61.6% (95% CI: 56.6-66.6%), and 50.9% (95% CI: 49.0-52.8%) for patients diagnosed in the pre-, immediate, and peri-pandemic periods respectively. Time for 80% NAC patients to have a surgery was 7.2 months in the immediate pandemic period, shorter than the 8.2 months in the pre-pandemic and 8.0 months in the peri-pandemic periods. CONCLUSIONS: In this large population-based study of BC patients in Ontario, we identified a delay in time to surgery in the immediate pandemic period that persisted into the peri-pandemic period. However, among patients receiving NAC there was a shorter wait time during the immediate pandemic and wait times for this group have returned to pre-pandemic levels. This is likely due to surgical prioritization of this group, despite pandemic related resource restrictions. Further research is needed to explore the regional variability and how use of neoadjuvant endocrine therapy interacted with surgical treatment timelines. Citation Format: Gary Ko, Amanda Roberts, Qing Li, Ning Liu, Toni Zhong, Eitan Amir, Anne Koch, Andrea Covelli, Vivianne Freitas, Emma Reel, Antoine Eskander, Tulin Cil. Delays in breast cancer surgery during the COVID-19 pandemic: A population-based analysis [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 PO3-23-02.

Use of neoadjuvant endocrine therapy with cyclin-dependent kinase 4/6 inhibitors to downstage inoperable, non-metastatic, oestrogen receptor positive, HER2-negative breast cancer

Use of neoadjuvant endocrine therapy with cyclin-dependent kinase 4/6 inhibitors to downstage inoperable, non-metastatic, oestrogen receptor positive, HER2-negative breast cancer

Abstract B122: Differential response to neoadjuvant endocrine therapy for Black and White women in NCDB

Abstract Introduction: Black/African American (BAA) women have 4x higher mortality from hormone receptor positive breast cancer (HR+BC) than White women. Despite this disparity, HR+BC across races is treated with relative uniformity: endocrine therapy. Previous studies have focused on the adjuvant setting. We examined use of neoadjuvant endocrine therapy (NET) in BAA and White women in the National Cancer Database (NCDB) and assessed treatment response by race. Methods: We queried the NCDB for women with clinical stage I-III HR+BC treated between the years 2004-2017 with NET. Patients receiving neoadjuvant chemotherapy and with unknown surgery or race were excluded. Time between initiation of NET and date of first operation was used to proxy duration of NET. Our primary objective was to compare in BAA and White women changes in tumor size and nodal status after NET, considering duration of treatment. Univariate and multivariable logistic regression was performed. Results: The final sample included 9,864 White and 1,090 BAA women. BAA women were disproportionately excluded for receipt of neoadjuvant chemotherapy (OR=1.8, 95%CI 1.6-1.9). Sociodemographic variables differed between the two groups with p<0.001, including payor status (12.8% BAA with Medicaid vs 5.2% White), income (33.8% BAA with <$38000 median household income vs 11.9% White), location (73.4% BAA living in metropolitan areas vs 55.4% White), and treatment facility (45.7% and 28.3% BAA at an academic center and community hospital respectively vs 32.7% and 37% White, respectively). Median duration of NET was higher in BAA (128 days) than Whites (114 days), p<0.001. After excluding those with unknown pT/N/M, 3,521 White and 365 BAA women were evaluated for NET response. Overall, 0.8% downstaged to pT0 or pTis and 0.9% upstaged to Stage IV disease. Women downstaged from only Clinical Stage I-II disease whereas all but 2 women upstaged from Stage II or higher. Compared to White women, BAA women were more likely to present as node positive (OR=1.6, 95%CI 1.3-2.1) or Stage III (OR=1.5, 95%CI 1.1-2.0) and be treated with NET for >24 weeks (OR=1.5, 95%CI 1.2-1.8). On multivariate analyses, compared to White women, BAA women were more likely to downstage to pT0/Tis. BAA women who downstaged to pT0/Tis had longer duration of NET than their White counterparts (median 241 vs 167.5 days, respectively); race was a significant predictor of downstaging on multivariate analysis adjusting for duration of NET and clinical stage (OR=2.85, p=0.016 for BAA). Compared to White women, BAA women were more likely to upstage to Stage IV on multivariate analysis despite being treated longer with NET and controlling for stage at presentation. Conclusion: This study offers important insight into the heterogeneity of HR+BC biology across races in response to NET. While longer duration of NET appears beneficial for BAA women presenting with lower stage clinical disease, it did not demonstrate benefit in BAA women with higher clinical stage. These findings suggest a dichotomous presentation of HR+BC biology in BAA women. Citation Format: Veronica Jones, Mary Schroeder, Mya Roberson, James De Andrade, Ingrid Lizarraga. Differential response to neoadjuvant endocrine therapy for Black and White women in NCDB [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B122.

Abstract 797: Role of ESR1 mutation in recurrence of tumorigenesis after therapeutic radiation

Abstract Acquired mutations in ESR1 gene that encodes for Estrogen Receptor (ER) are a common mechanism of acquired resistance to endocrine therapies in breast cancer. However, the role of such mutations in modulation of cell’s response to radiation therapy is poorly understood. In this study, we define the role of ESR1 mutations in altering response to radiation therapy in pre-clinical models of ER-positive breast cancer. To investigate whether ESR1 mutations influence cell’s response to radiation therapy, we employed ER-positive MCF7 and T47D cell lines which have been genome edited to knock-in two of the most common ESR1 mutations, such as Y537S and D538G, found in breast cancer patients. Clonogenic survival assays were carried out to characterize differences in radiation sensitivity of these cells. g-H2AX and Comet assays were employed to study the differences in residual unrepaired DNA damage following radiation in these cell lines. MCF7 cell line-derived xenografts harboring the wild type or mutant ESR1 were employed to study differences in radiation resistance of these tumors in vivo. We found that ER-positive cell lines harboring ESR1 mutations exhibited profound resistance to radiation therapy compared to cell lines harboring the wild type ESR1. These radioresistant cell lines also demonstrated significantly less unrepaired DNA damage following radiation therapy. We observed that mice harboring ESR1 mutant xenografts showed remarkable resistance to radiation therapy. We also observed that ESR1 mutations, which confer resistance to endocrine therapies, also confer profound resistance to radiation therapy. Our findings suggest that oligometastatic ER-positive breast cancer patients who are being treated with radiation therapy (such as those enrolled in NRG BR002 trial) may show significant differences in response to radiation therapy based on their ESR1 mutation status. Recent studies are also exploring the use of neo-adjuvant endocrine therapy in non-metastatic ER-positive breast cancer patients. It is conceivable that some of these patients may acquire ESR1 mutations under selective pressure of neoadjuvant endocrine therapy and may respond poorly to subsequent adjuvant radiation therapy. Overall, our findings support potential personalization of radiation treatments in breast cancer patients based on ESR1 mutation status, heralding an era of precision radiation oncology. Citation Format: S. M. Nashir Udden, Prasanna G. Alluri. Role of ESR1 mutation in recurrence of tumorigenesis after therapeutic radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 797.

96P PAM50-based ROR indexes as a tool to individualize the use of neoadjuvant endocrine therapy in ER+/HER2- breast cancer

Neoadjuvant endocrine therapy (NET) is an attractive scenario to find novel biomarkers in oestrogen receptor-positive/HER2-negative breast cancer (ER+/HER2- BC). In this context, PAM50 multigene panel has been validated as a relapse predictor. This study aims to determine if PAM50-derived risk of recurrence (ROR) indexes at diagnosis correlate with biomarkers of response to NET.

Neoadjuvant Endocrine Therapy for Operable Breast Cancer: A Retrospective Analysis of Real-World Use.

A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing the role of NET in breast cancer care. In a consecutive series of women with operable breast cancer who received NET for ≥28 days, associations of NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survival with clinicopathological factors were examined. NET objectives were reduction in surgical extent in 49 patients, avoidance of surgery in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1,923), 869.8 (range, 36-4,859), and 55.8 (range, 39-113) days, respectively, in these cohorts (success rate: 79.6%, 64.5%, and 100%, respectively), and the differences were significant. Among patients in the former two cohorts, progression-free survival was significantly better in patients with stage 0 or I disease, ductal carcinoma in situ or invasive ductal carcinoma, ≥71% estrogen receptor (ER) positivity, and the surgical extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly associated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high preoperative endocrine prognostic index at the time of surgery after NET. Better recurrence-free survival after surgery was significantly associated with high ER expression after NET or high progesterone receptor expression before or after NET. NET can help reduce surgical extent or avoid surgery in women with early breast cancer, ductal carcinoma, or high ER expression. NET may also aid in decisions related to postoperative systemic therapy to improve survival.

Delays in operative management of early-stage, estrogen receptor–positive breast cancer during the COVID-19 pandemic: A multi-institutional matched historical cohort study

BackgroundDuring the COVID-19 pandemic, guidelines recommended that breast cancer centers delay estrogen receptor–positive breast cancer surgeries with neoadjuvant endocrine therapy. We aimed to evaluate pathologic upstaging of breast cancer patients affected by these guidelines. MethodsFemale patients with stage I/II breast cancer receiving neoadjuvant endocrine therapy were prospectively identified and were matched to a historical cohort of stage I/II estrogen receptor–positive breast cancer patients treated with upfront surgery ≤35 days. Primary outcomes were pathologic T and N upstaging versus clinical staging. ResultsAfter matching, 28 neoadjuvant endocrine therapy and 48 control patients remained. Median age in each group was 65 (P = .68). Most patients (78.6% and 79.2%) had invasive ductal carcinoma with a clinical tumor size of 0.9 cm vs 1.7 cm (P = .056). Time to surgery was 68 days in the neoadjuvant endocrine therapy group and 26.5 days in the control (P < .001). A total of 23 neoadjuvant endocrine therapy patients (82.1%) had the same or lower pT-stage compared with 31 (64.5%) control patients (P = .115). Only 3 (10.7%) neoadjuvant endocrine therapy patients had increased pN-stage vs 14 (29.2%) control patients (P = .063). ConclusionDespite 2.5-times longer delays, patients with early-stage estrogen receptor–positive breast cancer receiving neoadjuvant endocrine therapy did not experience pathologic upstaging during the COVID-19 pandemic. These findings may support the use of neoadjuvant endocrine therapy in similar patients if delays to surgery are projected.

Bridging Endocrine Therapy for HR+/HER2- Resectable Breast Cancer: Is it Safe?

The COVID-19 pandemic has required new treatment paradigms to limit exposures and optimize hospital resources, including the use of neoadjuvant endocrine therapy (NAET) as bridging therapy for HR+/HER2-invasive tumors and DCIS. While this approach has been used in locally advanced disease, it is unclear how it may affect outcomes in resectable HR+/HER2- tumors. Women ≥18years diagnosed with in situ (Tis) or non-metastatic HR+/HER2- breast cancer from March-May 2019 and 2020 were included. Fisher's exact test and two-sample t test were used to compare baseline characteristics and surgical outcomes between strata. Sub-analysis was performed between patients who received primary surgery vs a bridging NAET approach. Despite similar clinical characteristics, patients in 2019 were more likely to have a surgery-first approach (75% vs 42%, P-value = .0007), receive surgery sooner (22 vs 29days, P-value < .001), and within 60days from diagnosis date (100% vs 85%, P-value = .0301). Neoadjuvant endocrine therapy was a more prevalent approach in 2020 (48% vs 7%, P-value < .0001). Rates of clinical to pathologic up-staging remained consistent across primary surgery vs bridging NAET subgroups (P-value = .9253). Pandemic-driven treatment protocols provide a unique opportunity to assess the utility of bridging endocrine therapy for resectable HR+/HER2- tumors. Differences in clinical and pathologic staging were similar across groups and did not appear to be affected by receipt of NAET. Our limited cohort demonstrates this strategic therapeutic avenue can optimize health care utilization and may be a reasonable approach when delaying surgery is preferred.

Effectiveness of a Short Duration of Neoadjuvant Endocrine Therapy in Patients with HR+ Breast Cancer—An NCDB Analysis (2004–2016)

BackgroundNational medical/surgical organizations have recommended the use of neoadjuvant endocrine therapy (NET) to bridge surgery delay of weeks to months for patients with hormone receptor positive (HR+) breast cancer during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The effects of NET of varying durations on pathologic response are unclear. Using the National Cancer Database (NCDB), we evaluated objective response to short (< 9 weeks), moderate (9–27 weeks), and long (> 27 weeks) duration of NET.Patients and MethodsThe study cohort included female patients diagnosed with nonmetastatic invasive HR+ breast cancer, stratifying by those who received NET versus no NET between 2004 and 2016. Pathologic response was grouped into four categories (complete, downstaged, stable, upstaged) by comparing clinical and pathologic staging data. Objective response to NET included complete, downstaged, and stable pathologic response. Clinical characteristics were compared using χ2 and analysis of variance (ANOVA) tests. Multivariable logistic regression was used to determine factors associated with NET use and objective response according to NET duration.ResultsA minority (1.2%) received NET in our cohort. Factors associated with NET use included older age, non-Black patients, more advanced clinical stage, higher comorbidity score, government insurance, and lobular histology. Objective response rate (ORR) was 56.7%, 52.1%, and 49.0% after short, moderate, and long NET duration, respectively.ConclusionShort NET duration did not result in an inferior ORR. Future study to evaluate the interaction between surgery delay and NET use on clinical outcome will provide insights into the safety of NET to bridge potential surgery delay in patients with HR+ breast cancer.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-021-10287-5.

How did the COVID crisis affect use of neoadjuvant therapy for patients with breast cancer?

e18708 Background: The COVID-19 pandemic has caused shifts in terms of cancer management, but the impact of this has not been well-elucidated in a contemporary cohort of patients in clinical practice in the US. We hypothesized that closure of operating rooms would increase the use of neoadjuvant therapy (NT) during the early pandemic period. Methods: The nationwide Flatiron Health database is a longitudinal electronic health record (EHR)-derived database, comprising de-identified, patient-level structured and unstructured data, curated via technology-enabled abstraction. These data originated from approximately 280 cancer clinics. We compared patients diagnosed with non-metastatic breast cancer during the early pandemic period (March 1 – June 30, 2020; group 1) with those diagnosed in the four month period prior (November 1, 2019 – February 29, 2020; group 2) and those diagnosed during the same period one year earlier (March 1 – June 30, 2019; group 3). Results: There were 174 patients in group 1, 277 in group 2, and 348 in group 3. Overall, 591 (74.1%) were ER/PR+HER2-, 100 (12.6%) were HER2+, and 106 (13.3%) were triple negative (TN). Patients in the three groups were equally likely to be ER/PR+HER2- (75.3% vs. 72.2% vs. 74.9%, p = 0.68), HER2+ (12.1% vs. 14.9% vs. 11%, p = 0.33), TN (12.6% vs. 12.7% vs. 14.2%, p = 0.83) and to be high risk by genomic testing (either Oncotype Dx or Mammaprint; p = 0.72). While there was no difference in the clinical stage (p = 0.36) nor patient age at diagnosis (p = 0.76) across the three groups, patients diagnosed during the early pandemic (group 1) were more likely to receive NT compared to those diagnosed one year earlier (group 3); 28.7% vs 16.4%, p &lt; 0.01 (see table). The use of NT differed between the three groups in the ER/PR+her2- (p &lt; 0.01) and her2+ patients (p = 0.05), but not in the TN patients (p = 0.61). There was no difference in the use of NT overall during the pandemic by geographic state (p = 0.32) nor practice setting (p = 0.23); NT was also similar by geographic state and practice setting when considering the ER/PR+HER2-, HER2+, and TNBC subsets. Conclusions: Despite similar clinicopathologic features as earlier time periods, there was an increased use of NT during the early pandemic when compared to the same period in the prior year. This was seen particularly in the ER/PR+HER2- group, suggesting an increased use of neoadjuvant endocrine therapy.[Table: see text]

Rate and predictors of nodal pathological complete response following neoadjuvant endocrine treatment in clinically biopsy-proven node-positive breast cancer patients

BackgroundData on effectiveness and optimal use of neoadjuvant endocrine therapy (NET) in clinically biopsy-proven node-positive breast cancer is lacking. This study examined the incidence of axillary pathological complete response (pCR) on NET in clinically biopsy-proven node-positive breast cancer patients. Secondary, patient and tumour characteristics, as well as the optimal duration of NET in relation to the occurrence of axillary pCR were investigated. Material and methodsPatients diagnosed with primary hormone receptor positive, HER2 negative breast cancer between 2014 and 2019, with at least one positive axillary lymph node (pathologically proven), treated with NET were selected from the Netherlands Cancer Registry. The incidence of axillary pCR in combination with patient, tumour and treatment characteristics was analysed. ResultsIn a population of 561 patients, an axillary pCR of 7.3% on NET was observed. Median length of treatment was 8.1 months in the patients without vs. 8.8 months in those with axillary pCR, with no statistically significant difference. A p-value <0.30 was found for age, histologic type, clinical tumour status, hormone receptor status and the type of NET in univariable analysis. After multivariable logistic regression analyses, none of these variables were independently associated with the likelihood of an axillary pCR. ConclusionThe rate of axillary pCR after NET in HR + HER2-clinically biopsy-proven node-positive breast cancer patients is low. Factors independently associated with the likelihood of an axillary pCR could not be identified. More research is warranted regarding optimizing the duration of NET and the prognostic value of residual disease in the axilla after NET.

Neoadjuvant endocrine therapy use in early stage breast cancer during the covid-19 pandemic.

PurposePhysician treatment preferences for early stage, estrogen positive breast cancer (ER + BC) patients were evaluated during the initial surge of the COVID-19 pandemic in the US when neoadjuvant endocrine therapy (NET) was recommended to allow safe deferral of surgery.MethodsA validated electronic survey was administered May–June, 2020 to US medical oncologists (MO), radiation oncologists (RO), and surgeons (SO) involved in clinical trials organizations. Questions on NET use included practice patterns for locoregional management following NET.Results114 Physicians from 29 states completed the survey—42 (37%) MO, 14 (12%) RO, and 58 (51%) SO. Before COVID-19, most used NET ‘rarely’ (49/107, 46%) or ‘sometimes’ (36, 33%) for ER + BC. 46% would delay surgery 2 months without NET. The preferred NET regimen was tamoxifen for premenopausal and aromatase inhibitor for postmenopausal women. 53% planned short term NET until surgery could proceed. Most recommended omitting axillary lymph node dissection (ALND) for one micrometastatic node after 1, 2, or 3 months of NET (1 month, N = 56/93, 60%; 2 months, N = 54/92, 59%; 3 months, N = 48/90, 53%). With longer duration of NET, omission of ALND decreased, regardless of years in practice, percent of practice in BC, practice type, participation in multidisciplinary tumor board, or number of regional COVID-19 cases.ConclusionMore physicians preferred NET for ER + BC during the pandemic, compared with pre-pandemic times. As the duration of NET extended, more providers favored ALND in low volume metastatic axillary disease. The Covid-19 pandemic affected practice of ER + BC; it remains to be seen how this may impact outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-021-06153-3.

Abstract SS2-05: Emerging from COVID-19 pandemic: Provider perspective on use of neoadjuvant endocrine therapy (NET) in early stage hormone receptor positive breast cancer

Introduction During the coronavirus 2019 (COVID-19) pandemic in USA, NET use has been recommended to allowsafe deferral of surgical treatment in early stage, estrogen receptor positive breast cancer (ER+BC) In suchcircumstances, after NET use there is limited guidance on locoregional treatment, especially with management of the axilla We aimed to evaluate patterns of care in early stage ER+BC during the first several months of theCOVID-19 pandemic Method A cross-sectional, 30-item survey was developed using a standardized surveydevelopment framework The survey was administered May 8 - June 12, 2020 to a convenience sample of medicaloncologists (MO), radiation oncologists (RO), and surgeons (SO) - breast committee members of two nationalcooperative groups (Alliance and SWOG) with additional participation through chain referrals Providers were presented with general questions on NET use before and during the pandemic They were asked their propensity foromitting axillary lymph node dissection (ALND) after NET if 1 micrometastatic node is found on sentinel lymph nodebiopsy, based on duration of NET Results 114 providers from 29 US states completed the survey - 42 (37%) MO, 14(12%) RO, and 58 (51%) SO, the majority (N=73/96, 76%) with practices dedicated ≥ 75% to BC, at NCI designatedcomprehensive cancer centers 52% (N=48/94) and in large cities (N=49/94, 52%) Prior to COVID-19, most rarely(N=49/107, 46%) or sometimes (N=36, 33%) used NET for early stage ER+BC Nearly half were willing to delay surgery up to 2 months (46%) and 3 months (21%) without use of NET (Table 1, p<0 05) Most providers wouldperform a genomic assay on the biopsy specimen on all or select patients prior to NET initiation, more frequently byMO compared to RO and SO (90% vs 75% and 60%, p<0 05) The most preferred regimen was tamoxifen (withoutovarian suppression) for premenopausal patients and aromatase inhibitor for postmenopausal patients Mostplanned to use NET for as little time as possible until surgery could proceed When stratified by specialty, more MOstated they would vary the duration of therapy based on patient's risk of cancer progression Most providersrecommended omitting ALND after 1, 2, or 3 months of NET (1 month N=56/93, 60%;2 months N=54/92, 59%;3months N=48/90, 53%) With longer duration of therapy, the propensity for omitting ALND decreased (definitely omitafter 6 months N=25/91, 27%;probably omit after 6 months N=38/91, 42%;definitely omit after 1 year N=26/92,28%;probably omit after 1 year N=29/92, 32%) Omitting ALND was not associated with provider's years in practice,percent of practice dedicated to BC, practice type or setting, participation in multidisciplinary tumor board, or numberof COVID-19 cases in the provider's practicing state ConclusionMost providers changed their management of early stage ER+BC during the COVID-19 pandemic by utilizing NET until surgery could proceed As the duration of NET extended, more providers favored ALND in low volume axillary metastatic disease in early stage ER+BC Additional data to inform the care on post-NET locoregional management is needed

COVID-19 Pandemic: Changes in Care for a Community Academic Breast Center and Patient Perception of Those Changes.

BackgroundPhiladelphia and its suburbs were an epicenter for the initial COVID-19 outbreak. Accordingly, alterations were made in breast cancer care at a community hospital.MethodsThe authors developed a prospective database of all the patients with invasive or in situ breast cancer between March 1 and June 15 at their breast center. Any change in a breast cancer plan due to the pandemic was documented, and the patients were grouped into two cohorts according to whether a change was made (CTX) or no change was made (NC) in their care. The patients were asked a series of questions about their care, including those in the Generalized Anxiety Disorder two-item questionnaire (GAD-2), via telephone.ResultsThe study enrolled 73 patients: 41 NC patients (56%) and 32 CTX patients (44%). The two cohorts did not differ in terms of age, race, or stage. Changes included delay in therapy (15.1%) and use of neoadjuvant endocrine therapy (NET, 28.8%). The median time to surgery was 24 days (interequartile range [IQR], 16–45 days) for the NC patients and 82 day s (IQR, 52–98 days) for the CTX patients (p ≤ 0.001). The median duration of NET was 78 days. The GAD-2 showed anxiety positivity to be 29.6% for the CTX patients and 32.4% for the NC patients (p = 1.00). More than half (55.6%) of the CTX patients believed COVID-19 affected their treatment outlook compared with 25.7% of the NC patients (p = 0.021).ConclusionsA prospective database captured changes in breast cancer care at a community academic breast center during the initial phase of the COVID-19 pandemic. 44% of patients experienced a change in breast cancer care due to COVID-19. The same level of anxiety and depression was seen in both change in therapy (CTX) and no change (NC). 55.6% of CTX cohort believed COVID-19 affected their treatment outlook.

Abstract P1-09-01: ESR1 mutations confer radiation resistance in breast cancer

Abstract Background: Acquired mutations in oncogenic drivers in response to systemic therapies is a common mechanism of treatment resistance. How such mutations alter response to radiation therapy is poorly understood. The increasing adoption of radiation therapy in the treatment of oligometastatic disease further amplifies the need to define the role of such mutations in modifying response to radiation therapy. Over 70% of breast cancers are Estrogen Receptor (ER)-positive. Endocrine therapies, which block ER signaling, are the mainstay in the treatment of such cancers. Acquired mutations in the gene encoding for ER (ESR1) are a common mechanism of acquired resistance to endocrine therapies in metastatic breast cancer. In this study, we define the role of ESR1 mutations in altering response to radiation therapy in pre-clinical models of ER-positive breast cancer. Methods: To test if ESR1 mutations influence response to radiation therapy, we employed ER-positive MCF7 and T47D cell lines which have been genome edited to knockin two of the most common ESR1 mutations found in breast cancer patients (Y537S and D538G). Clonogenic survival assays were carried out to characterize differences in radiation sensitivity of these cells. γ-H2AX and Comet assays were employed to study the differences in residual unrepaired DNA damage following radiation in these cell lines. MCF7 cell line-derived xenografts harboring the wild type or mutant ESR1 were employed to study differences in radiation resistance of these tumors in vivo. Results: ER-positive cell lines harboring ESR1 mutations exhibited profound resistance to radiation therapy compared to cell lines harboring the wild type ESR1. These radioresistant cell lines also demonstrated significantly less unrepaired DNA damage following radiation therapy. Mice harboring ESR1 mutant xenografts showed remarkable resistance to radiation therapy. Conclusion: ESR1 mutations, which confer resistance to endocrine therapies, also confer profound resistance to radiation therapy. ESR1 mutations have been primarily reported in metastatic ER-positive breast cancer patients with prior history of treatment with endocrine therapies. Our findings suggest that oligometastatic ER-positive breast cancer patients who are being treated with radiation therapy (such as those enrolled in NRG BR002 trial) may show significant differences in response to radiation therapy based on their ESR1 mutation status. Recent studies are also exploring the use of neo-adjuvant endocrine therapy in non-metastatic ER-positive breast cancer patients. It is conceivable that some of these patients may acquire ESR1 mutations under selective pressure of neoadjuvant endocrine therapy and may respond poorly to subsequent adjuvant radiation therapy. Finally, our findings support potential personalization of radiation treatments in breast cancer patients based on ESR1 mutation status, heralding an era of precision radiation oncology. Citation Format: Nashir Udden, Qian Wang, Prasanna G Alluri. ESR1 mutations confer radiation resistance in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-09-01.

Treatment effect of neoadjuvant endocrine therapy compared to neoadjuvant chemotherapy on breast cancer outcomes.

e12630Background: Over the last decade, there has been increased use of neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor (HR) positive breast cancer. Small clinical trials ...

Using a Neoadjuvant Approach for Evaluating Novel Therapies for Patients With Breast Cancer.

Preoperative systemic therapy, though primarily used to downstage breast cancers, can offer, using pathologic complete response (pCR) as an endpoint, a rapid assessment of efficacy of a given therapeutic approach, particularly in triple-negative (TNBC) and HER2-positive breast cancers. Recently, this approach resulted in the approval of pertuzumab for HER2-positive cancers, in a considerably quicker timeline than would have been possible with its assessment in the adjuvant setting. However, the use of preoperative systemic therapy remains controversial, as the higher response rates noted with newer approaches have not routinely translated into improved longer-term outcomes, nor have they been confirmed in larger adjuvant trials. Almost all trials have demonstrated that pCR is a robust prognostic marker in patients with TNBC and HER2-positive cancers, so part of this discrepancy may be due to inadequate power in the preoperative trials and/or due to the heterogeneous nature of breast cancers. PCR following preoperative chemotherapy is not prognostic in many hormone receptor (HR)-positive breast cancers, especially those with a luminal A phenotype, which typically has minimal response to chemotherapy. Given this lack of response to chemotherapy, there is considerable interest in the use of neoadjuvant endocrine therapy (NET). The rate of pCR to NET in HR-positive cancers is low, leading to the use of surrogate markers, including changes in Ki-67 and the preoperative endocrine prognostic index (PEPI) score, as biomarkers of efficacy. Overall, the use of neoadjuvant approaches offers a rapid assessment of efficacy of novel therapies and remains a useful research tool for drug evaluation.

Duration of neoadjuvant endocrine therapy and breast cancer outcomes.

e12129 Background: Interest in the use of neoadjuvant endocrine therapy (NET) has increased over the past decade, and recent studies have demonstrated similar response rates compared to neoadjuvant chemotherapy. We examined the associations between duration of NET and type of surgery and change from clinical stage to pathologic stage. Methods: We used the National Cancer Data Base to identify women diagnosed with stage II-III, ER and/or PR positive breast cancer who received endocrine therapy from 2004-2014 and underwent surgery. We classified patients according to timing and duration of NET. We performed logistic regression to examine the impact of NET duration on likelihood of 1) receiving breast conserving surgery (BCS) versus mastectomy and 2) being downstaged. Downstaging was defined as pathologic stage lower than clinical stage and upstaging as pathologic stage higher than clinical stage. Results: In our sample of 159,676 patients, 6584 received NET (4.1%). NET was more frequently used in older women with multiple comorbid conditions, larger tumors, and higher nodal stage. The highest rates of NET were in academic/research or integrated network cancer programs. Of patients who underwent NET, 26.5% received it for ≤3 months, 41.0% for 3-6 months, 27.7% for 6-12 months, and 4.9% for 12-24 months. Patients who received NET for 3-6, 6-12, and 12-24 months were all significantly more likely to receive BCS versus mastectomy than patients who did not receive NET (Table). Patients who underwent NET compared to adjuvant endocrine therapy were more likely to be downstaged (Table). Conclusions: The most common duration of NET was 3-6 months, but &gt;26% of patients received NET for less than 3 months. Longer durations of NET were strongly associated with BCS and downstaging. Further research is needed to determine the population of patients mostly likely to benefit from NET and the optimal length of treatment. [Table: see text]

A Waiting Game: The Use of Neoadjuvant Endocrine Therapy as a Bridge to Surgery

A Waiting Game: The Use of Neoadjuvant Endocrine Therapy as a Bridge to Surgery