Estrogen Receptor Positive Disease Research Articles

Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up.

Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.

The Use of Sentinel Lymph Node Biopsy in Patients Undergoing Mastectomy for DCIS

BackgroundCurrent guidelines do not recommend routine sentinel node biopsy (SLNB) for ductal carcinoma in situ (DCIS), except in the setting of mastectomy or microinvasive disease. This study aimed to evaluate national SLNB utilization in women undergoing upfront mastectomy for DCIS, identify predictors of SLNB utilization, and determine the percentage with a positive SLNB. MethodsA retrospective cohort analysis was performed using the NCDB of women with clinical DCIS who underwent upfront mastectomy between 2012–2017. Demographic and clinicopathologic variables were compared between patients who underwent SLNB and those who did not. Multivariate logistic regression models were used to identify factors associated with SLNB utilization and positive SLNB. Results38,973 patients met inclusion criteria: 34,231 (88%) underwent SLNB and 4,742 (12%) had no surgical axillary staging. Most patients were age 50–69 (51%), non-Hispanic White (71%), with private insurance (66%). On multivariate analysis, older patients were less likely to receive SLNB (p<0.01), while patients with higher grade DCIS were more likely to undergo SLNB (p<0.01). In those who underwent SLNB (n=34,231), only 1,149 (3.4%) had nodal involvement. Non-Hispanic Black patients had increased odds of a positive SLNB (p<0.01), while those with estrogen receptor positive disease were less likely to be node positive (OR 0.68, p<0.001). ConclusionsWhile 88% of patients had a SLNB, only 3.4% were found to be node positive. Given this low rate, it is reasonable to consider SLNB omission in select patients with low grade, hormone receptor positive DCIS undergoing upfront mastectomy. Micro AbstractThe NCDB was used to examine SLNB utilization in patients with DCIS undergoing upfront mastectomy. Findings indicated low rates of nodal involvement and that hormone receptor-negative and high-grade DCIS were associated with positive SLNB, suggesting it is reasonable to consider SLNB omission for select populations.

Abstract PO2-08-09: Prevalence of germline genetic variants in breast cancer susceptibility genes among patients with metaplastic breast cancer

Abstract Background: Pathogenic or likely pathogenic variants (PV) in breast cancer (BC) susceptibility genes are present in approximately 5-10% of individuals with breast cancer and approximately 13-15% of those with triple-negative breast cancer (TNBC). Identifying patients with PV in BRCA1 and BRCA2 can inform selection of appropriate candidates for poly(ADP-ribose) polymerase inhibitors (PARPi), which have improved progression-free and overall survival in the metastatic and adjuvant settings, respectively. Metaplastic breast cancer (MpBC) is a rare, aggressive subtype of breast cancer that is often triple-negative and refractory to chemotherapy. To date, limited data describe germline genetic findings in patients with MpBC. Methods: We conducted a retrospective chart review including patients with pathology results at the Hospital of the University of Pennsylvania from 2021 through May 2023 demonstrating MpBC. Germline genetic test results and tumor histopathologic characteristics including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were evaluated. Descriptive statistics as well as two-tailed t tests were used for data analysis. Results: Of 89 patients identified with MpBC, 51 had germline genetic testing results available for review. Nine patients (17.6%) had MpBC with PV in BC predisposition genes (PV-MpBC) and 42 (82.4%) had PV-negative MpBC (PVneg-MpBC). Seven patients (13.7%) had a PV in BRCA1, 1 (2.0%) in BRCA2, and 1 (2.0%) in CHEK2. Median age at diagnosis was 45 years for patients with PV-MpBC and 56.5 years for those with PVneg-MpBC (p=0.005). Among patients with PV-MpBC, 6 (66.7%) had ER and PR negative disease by ASCO-CAP guidelines and 3 (33.3%) had ER and/or PR positive disease. Among patients with PVneg-MpBC, 31 (73.8%) had ER and PR negative disease and 11 (26.2%) had ER and/or PR positive disease. All 9 patients with PV-MpBC had HER2-negative disease, one (11.1%) of whom had HER2-low disease. Among patients with PVneg-MpBC, 40 (95.2%) had HER2-negative disease, two (4.8%) of whom had HER2-low disease, and 2 (4.8%) had HER2-positive BC. Conclusions: The frequency of PV in breast cancer susceptibility genes among patients with MpBC is comparable to, and possibly higher than, the reported rates of such PV in patients with TNBC, for whom genetic testing is recommended. If confirmed in a larger dataset, germline testing should be considered for all patients with MpBC regardless of ER, PR, and HER2 status, as findings may help identify candidates for PARPi therapy and genetically-directed clinical trials. Citation Format: Kaitlin Demarest, Anupma Nayak, Payal Shah. Prevalence of germline genetic variants in breast cancer susceptibility genes among patients with metaplastic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-09.

Abstract PO5-05-13: Clinical utility of whole body low dose computed tomography for detecting bone metastasis in breast cancer patients: A cross sectional study

Abstract Clinical utility of Whole Body Low Dose CT scan for detecting bone metastasis in Breast cancer patients: A cross sectional study Background: Skeletal scintigraphy (Bone scan) is the imaging of choice to detect bone metastasis in locally advanced and metastatic breast cancer patients. Nuclear medicine facilities are however limited in their availability. As an alternative diagnostic modality to bone scan, we studied the diagnostic capability of Whole-Body Low Dose CT (WBLDCT) scan for detection of bone metastasis in these patients. Materials and Method: This cross-sectional study was conducted from November 2021 to May 2023 at a tertiary healthcare center in India with an aim to study the clinical applicability of whole-body low dose computed tomography scan for detecting bone metastasis in patients with breast cancer. Breast cancer patients with primary tumor measuring 5cm or more, pathologically proven axillary lymph node metastasis, Stage III/IV disease, symptoms attributable to metastasis and suspected disease recurrence were included. All patients underwent WBLDCT and Bone scan within a period of about 2 weeks. WBLDCT was done during the same time as conventional dose CT scan was being done as part of metastatic workup. WBLDCT acquisition protocol was set in CT scan machine by modulating the technical parameters like Care dose 4D-automated, Care kV semi, rotation time &amp; noise index. The image analysis was performed by Radiologist and Nuclear medicine experts in a blinded fashion. Data was recorded in MS Excel sheet. Sensitivity, specificity, positive and negative predicative value, and concordance rates were calculated using SPSS software ver 25.0. Agreement amongst WBLDCT and Bone scan was calculated using Inter-rater agreement. p value &amp;lt; 0.05 was taken as significant. Results: 110 patients were enrolled in this study. The mean age of participants was 48.5 years and three fourth had stage III disease at presentation. Estrogen receptor positive disease was seen in 43.64% participants while 30% were triple negative. Her2neu positive disease was seen in 27.27% patients. Bone scan couldn’t be done in 03 patients who deferred treatment (these had no bone metastasis on WBLDCT). Both bone scan and WBLDCT detected bone metastasis in 19 patients. Bone scan picked up additional metastasis in three patients which were missed on WBLDCT. WBLDCT detected bone metastasis additionally in three patients which were not detected on Bone scan. Multiple lesions were most seen in vertebrae in 38.5% and 28.6% on bone scan and WBLDCT respectively. The sensitivity and specificity of WBLDCT for detection of bone metastasis was 86.36% and 96.47% respectively. The concordance rate between Bone scan and WBLDCT scan was 94.39% with an Inter-rater Kappa(k) quotient for agreement of 0.828 (p&amp;lt; 0.0001). Conclusion: WBLDCT scan has comparable diagnostic capability to skeletal scintigraphy in detecting bone metastasis in breast cancer and may be a useful alternative specially in resource limited settings. Table 1: Sensitivity, specificity, positive predictive value and negative predictive value of WBLDCT for detection of metastasis Variables Values Sensitivity (95% CI) 86.36% Specificity (95% CI) 96.47% AUC (95% CI) 0.91 Positive Predictive Value (95% CI) 86.36% Negative Predictive Value (95% CI) 96.47% Diagnostic accuracy 94.39% Inter-rater agreement (kappa) 0.828 Citation Format: Lipton Mitra, Suhani Suhani, Ankur Goyal, Rakesh Kumar, Mohit Joshi, Hemanga Bhattacharjee, Haresh KP, Raju Sharma, Rajinder Parshad. Clinical utility of whole body low dose computed tomography for detecting bone metastasis in breast cancer patients: A cross sectional 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 PO5-05-13.

Abstract PO4-02-05: Elevated tumor to aorta ratio of Hounsfield units and late recurrence in patients with estrogen receptor positive breast cancer

Abstract Background) More than half of the recurrent disease in breast cancer will happen more than 5 years after initial diagnosis in breast cancer, especially in patients with ER positive disease. Higher proportions of late recurrence lead to escalated treatment and/or or extended treatment for high risk patients. However, it is unclear what characteristics make whom as high risk patients. This study aimed to assess initial tumor vascularity as a prognostic marker for late recurrence. Methods) Female patients with estrogen receptor positive breast cancer who were diagnosed breast cancer between 2003 and 2018 and disease-free at 5 years after primary breast cancer at Wonju Severance Hospital, Korea, were included. Clinocopathological characteristics were collected. Hounsfield units(HU) on contrast-enhanced computed tomography(CT) was used as a marker indicating tumor vascularity. Tumor to aortic arch ratio(TAR) of HU on contrast enhanced CT was applied to enhance objectivity of measurement. Patients were categorized according to the cut-off values retrieved from the receiver operating characteristic curve. Kaplan-Meier curves were generated to compare recurrence-free survival (RFS) and overall survival (OS). Hazard ratio(HR) with confidence interval(CI) was derived with Cox’s proportional hazard model to analyze univariate and multivariate risk factors. Results) The final cohort included 451 patients with a mean age of 56.21 ± 11.2 (22-83) years. Two third of patients had estrogen receptor positive disease and a quarter of patients had HER2 overexpressed disease. Initial TAR was 0.345 ± 0.108 (range, 0.062 - 1.114). Patients with recurrence free survival(RFS)-related events had significantly higher TAR than patients who did not(0.39 ± 0.097 vs. 0.34 ± 0.108, p=0.012). Patients with overall survival(OS)-related events also had higher TAR than patients who did not(0.408 ± 0.096 vs. 0.342 ± 0.107, p=0.002). Cutoff value of 0.408 was driven from area under the receiver operating characteristic curve. Patients with TAR higher than 0.408 showed significantly worse RFS(p=0.001) and OS(p&amp;lt; 0.001) than patients who had TAR equal or lower than 0.408. Hazard ratio(HR) of TAR in late recurrence was 6.17 (CI, 4.89 – 9.23, p=0.003), suggesting it is an independent factor. Other independent factors were age (HR, 1.502; CI, 10.14 – 10.91; p=0.006), tumor size (HR, 1.268; CI, 1.071 – 1.502; p=0.006), and metastatic nodal disease (HR, 2.770; CI, 1.176 – 6.526; p=0.020). Conclusion) TAR of primary tumor was significantly related with patients RFS and OS. Patients with high TAR larger than 0.408 showed worse RFS and OS than patients who did not. According to the Cox proportional hazard model, TAR was an independent factor along with age, tumor size, and metastatic nodal disease, suggesting late recurrence may rather be influenced by clinical factor Citation Format: Airi Han, Hyang Suk Choi, Seok Hahn, In-jeoung Cho, Seung Taek Lim, Jong-In Lee. Elevated tumor to aorta ratio of Hounsfield units and late recurrence in patients with estrogen receptor positive 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 PO4-02-05.

Abstract LB009: Unveiling the significance of DARPP-32 and its partners, including GRB7 and DKK1, in breast cancer: Integrative insights from patient data and cell line transcriptomics

Abstract DARPP-32 plays a crucial role in regulating both protein-phosphatase-1 (PP-1) and protein kinase A (PKA), its function being reliant on its phosphorylation status. We have previously demonstrated that low DARPP-32 expression is associated with adverse survival of breast cancer patients, particularly those with oestrogen receptor (ER) positive disease; however, there is limited information on how DARPP-32 may alter breast cancer cell behaviour. We have recently published an integrative approach using patient data and cell line transcriptomics to understand the role of DARPP-32 in breast cancer. We analysed the transcriptome of T47D ER positive breast cancer cells following DARPP-32 knockdown, including treatments in combination with 17β-estradiol or PKA inhibitor fragment (6-22) amide. 202 differentially expressed transcripts were identified in DARPP-32 knock down cells and treatment of these cells with 17β-estradiol or PKA inhibitor fragment (6-22) amide led to the differential expression of 193 and 181 transcripts respectively. Differentially expressed transcripts were compared with genes identified as associated with DARPP-32 expression in 1980 breast cancer patients within the METABRIC cohort using an Artificial Neural Network approach (ANN). Several genes overlapped with those identified from cell line transcriptomics, including PTK7, TRAF5, and KLK6. Both DKK1 and GRB7 were identified as genes associated with DARPP-32 expression in patients using ANN, therefore protein expression was determined in a large cohort of early-stage breast cancer patients (n&amp;gt;1000). We demonstrated that DKK1 and GRB7 protein expression was significantly correlated with DARPP-32 Threonine-34 phosphorylation levels within the same samples (all P&amp;lt;0.05). We have now applied an ANN-based integrative data mining approach to identify genes with the largest effect on other genes resulting in an interactome map, which was based on genes identified within the cell line transcriptomics and original ANN. 1878 genes were identified for inclusion within an interactome map in the total patient cohort, whereas 1003 were identified in ER negative disease alone and 2144 in ER positive disease alone. Pathway enrichment analysis identified the ubiquitin proteosome pathway, the insulin pathway-protein kinase B signalling cascade and the RAS pathway. This study underscores the significance of DARPP-32, a central molecular switch, in breast cancer, elucidating its impact on patient prognosis and highlighting potential molecular targets for therapeutic intervention. The integrative approach combining patient data with cell line transcriptomics provides insights into the complex mechanisms underlying breast cancer progression and opens avenues for further research and targeted interventions. Citation Format: Behnaz Saidy, Richa Vasan, Megan-Rose Greener, Rosie Durrant, Adelynn Immanuel, Andrew Green, Emad Rakha, Ian Ellis, Graham Ball, Stewart Martin, Sarah J. Storr. Unveiling the significance of DARPP-32 and its partners, including GRB7 and DKK1, in breast cancer: Integrative insights from patient data and cell line transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB009.

Racial disparities in initiation of chemotherapy among breast cancer patients with discretionary treatment indication in the state of Georgia

PurposeThe majority of breast cancer patients are diagnosed with early-stage estrogen receptor (ER) positive disease. Despite effective treatments for these cancers, Black women have higher mortality than White women. We investigated demographic and clinical factors associated with receipt of chemotherapy among those with a discretionary indication who are at risk for overtreatment.MethodsUsing Georgia Cancer Registry data, we identified females diagnosed with ER positive breast cancer who had a discretionary indication for chemotherapy (2010–2017). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associating patient demographic and clinical characteristics with chemotherapy initiation overall, and comparing non-Hispanic Black (NHB) with non-Hispanic White (NHW) women within strata of patient factors.ResultsWe identified 11,993 ER positive breast cancer patients with a discretionary indication for chemotherapy. NHB patients were more likely to initiate chemotherapy compared with NHW women (OR = 1.41, 95% CI: 1.28, 1.56). Race differences in chemotherapy initiation were pronounced among those who did not receive Oncotype DX testing (OR = 1.47, 95% CI: 1.31, 1.65) and among those residing in high socioeconomic status neighborhoods (OR = 2.48, 95% CI: 1.70, 3.61). However, we observed equitable chemotherapy receipt among patients who received Oncotype DX testing (OR = 0.90, 95% CI: 0.71, 1.14), were diagnosed with grade 1 disease (OR = 1.00, 95% CI: 0.74, 1.37), and those resided in rural areas (OR = 1.01, 95% CI: 0.76, 1.36).ConclusionWe observed racial disparities in the initiation of chemotherapy overall and by sociodemographic and clinical factors, and more equitable outcomes when clinical guidelines were followed.

21-gene recurrence score in predicting the outcome of postoperative radiotherapy in T1-2N1 luminal breast cancer after breast-conserving surgery

BackgroundIn those with one to three positive lymph nodes (N1) breast cancer (BC), the 21-gene recurrence score (RS) classification can be referred for decision-making on adjuvant chemotherapy. This study aimed to investigate the effect of RS in predicting the survival benefit of postoperative radiotherapy (PORT) in T1-2N1 BC with estrogen receptor-positive and human epidermal growth factor receptor 2-negative disease after breast-conserving surgery (BCS). MethodsWe included patients with BC and available RS data from the Surveillance, Epidemiology, and End Results Oncotype DX database. The chi-square test, Kaplan-Meier method, propensity score matching (PSM) as well as multivariable Cox proportional hazard analyses were used for statistical analyses. ResultsWe included 6509 patients in the analysis. Of these patients, 5302 (85.5%) were treated with BCS + PORT, and 207 (15.5%) had BCS alone. There were 1419 (21.8%), 4319 (66.4%), and 771 (11.8%) patients being low-, intermediate-, and high-risk RS, respectively. After PSM, PORT was significantly associated with a 5-year overall survival (OS) advantage (95.1% vs. 90.5%, P < 0.001) compared to those without PORT, which similar breast cancer-specific survival (BCSS) was found between the treatment arms (P = 0.126). The sensitivity analyses showed that PORT was not associated with a better BCSS (P = 0.472) and OS (P = 0.650) than those without PORT in the low-risk RS cohort. However, PORT was associated with a better BCSS (P = 0.031) and OS (P < 0.001) compared to those without PORT in the intermediate/high-risk RS cohorts. ConclusionsOur study highlights the possible role of the RS in predicting the outcome of PORT in T1-2N1 luminal BC patients undergoing BCS.

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes. We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan-Meier methods to characterize 3-year breast cancer risk in patients without upgrade. Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5-23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8-22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3-26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%). Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

Imaging Changes and Outcomes of Patients Undergoing Active Monitoring for Ductal Carcinoma In Situ: Seven-Year Follow-up Study

Rationale and ObjectiveTo determine the imaging changes and their associated positive predictive value (PPV) for invasive breast cancer in women undergoing active monitoring for DCIS. Materials and MethodsIn this seven-year follow-up retrospective IRB-exempted cohort study, we reviewed patients diagnosed with DCIS who elected active monitoring between 2003 to 2022 at a single academic institution. Imaging characteristics, histopathology at initial diagnosis, and subsequent follow-up were recorded. Low-risk DCIS was defined as low or intermediate grade and hormone receptor (HR) positive (estrogen and/or progesterone receptor positive) disease diagnosed in women at least 40 years of age. Progression was defined as subsequent ipsilateral invasive breast cancer diagnosis. ResultsThere were 39 patients with a median age of 58.4 years (IQR: 51.1 – 69.6 years) and a median follow-up of 4.3 years (range: 0.6-16.4 years). Nearly two thirds of patients (64%, 25/39) had stable imaging (range: 0.6-16.4 years) and remained progression-free during active monitoring. Among the remaining 14 patients (36%) there were 24 imaging findings which prompted 22 subsequent core needle biopsies (range: 1-3 biopsies per patient) and two surgical biopsies. The positive predictive value (PPV) of invasive cancer was 29% (7/24) overall and 38% (3/8) for masses, 33% (3/9) for calcifications, 17% (1/6) for non-mass enhancement, and 0% (0/1) for architectural distortion. ConclusionsOf the radiographic changes prompting an additional biopsy, development of a new mass (38%) and new calcifications (33%) had the highest PPV for invasive progression. Close imaging follow-up should be a critical component for patients undergoing monitoring for DCIS.

Tumor Characteristics of Bilateral Breast Cancer Compared with Unilateral Breast Cancer.

Bilateral breast cancer (BC) has an incidence of 1 to 3 %. This study aimed to describe the clinicopathologic characteristics and management of bilateral BC, estimate disease-free survival (DFS), and compare DFS with unilateral BC. A retrospective analysis was performed for patients who hadbilateral invasive BC or unilateral invasive BC and contralateral ductal carcinoma in situ (DCIS) treated at Mayo Clinic Rochester from 2008 to 2022. A 4:1 matched cohort of patients with unilateral invasive BC was used for comparison. The groups were compared using Wilcoxon rank-sum or chi-square tests. Disease-free survival was analyzed using the Kaplan-Meier method and log-rank test, with Cox proportional hazards regression used for multivariable analysis. The study identified 278 cases of bilateral breast cancer (177 cases of bilateral invasive cancer and 101 cases of unilateral invasive cancer with contralateral DCIS), representing 4.1 % of invasive BCs. Biologic subtype was concordant between sides in 79.8 % of the patients. Initial surgery was bilateral mastectomy for 76.6 %, bilateral lumpectomy for 20.5 %, and unilateral mastectomy with unilateral lumpectomy for 2.9 % of the patients. Pathogenic variants in breast cancer predisposition genes were present in 21.7 % of those tested. The patients who had bilateral BC presented with a higher cT category than the patients who had unilateral BC (p = 0.02), and a higher proportion presented with ILC (17.3 % vs 10.9 %; p = 0.004), estrogen receptor-positive (ER+) disease (89.2 % vs 84.2 %; p = 0.04), multicentric/multifocal disease (37.1 % vs 24.3 %; p < 0.001), breast cancer pathogenic variant (21.7 % vs 12.4 %; p = 0.02), and palpable presentation (48.2 % vs 40.8 %; p = 0.03). The patients with bilateral BC showed DFS similar to that for the unilateral BC cohort (p = 0.71). Bilateral BCs most commonly are biologically concordant between sides. Bilateral BC presented more commonly with larger tumors, lobular histology, ER+ status, multicentricity or multifocality, pathogenic variant, and palpable disease. Bilateral BC is not associated with worse DFS than unilateral BC.

Accelerated Partial Breast Irradiation for HER2-Positive Early-Stage Breast Cancer

HER2-positive (HER2+) breast cancer historically exhibited the most adverse local outcomes and, consequently, has had limited representation among trials of partial breast irradiation (PBI). We hypothesized that with contemporary HER2-targeted agents, patients may now exhibit excellent disease control outcomes after adjuvant PBI. Using a prospectively maintained institutional database, we identified patients with HER2+ breast cancer treated with breast conserving surgery (BCS) and PBI from 2000 to 2022. Salient clinicopathologic and treatment parameters were collected. All patients received external beam PBI to 40 Gy in 10 daily fractions. Cumulative incidence functions were calculated to estimate the incidence of local recurrence (LR) with the competing risk of death. We identified 1248 patients who underwent PBI at our institution, of whom the study cohort comprised 52 (4%) with HER2+ breast cancer (median age, 64 years; range, 44-87). Nearly all had T1 tumors (98%; median size, 12 mm [range, 1-21 mm]). Most had estrogen receptor positive disease (88%), and all patients had negative surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. Forty-two (81%) received chemotherapy; 40 (77%), hormone therapy; and 42 (81%), HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range, 7-226 months for each patient), we observed 2 LR events at 14 and 26 months, respectively, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any breast-specific mortality events. Two deaths were observed, both without evidence of disease. Among a cohort of patients with HER2+ early-stage breast cancer managed with BCS and PBI, we observed a 2-year LR rate of 3.8%, with no regional or distant recurrences and excellent overall survival. These findings require confirmation with longer follow-up among larger cohorts but appear consistent with the excellent results of contemporary randomized trials of PBI unselected for HER2 status.

Prediction of negative axillary node clearance by sentinel node-positive to total node ratio: a retrospective cohort study.

Increasing evidence suggests that de-escalation of axillary surgery is safe, without significantly impacting patient outcome. Obtaining positive lymph nodes at a sentinel lymph node biopsy (SNB) can guide decisions toward the requirement of axillary nodal clearance (ANC). However, methods to predict how many further nodes will be positive are not available. This study investigates the feasibility of predicting the likelihood of a negative ANC based on the ratio between positive nodes and the total number of lymph nodes excised at SNB. Retrospective data from January 2017 to March 2022 was collected from electronic medical records. Patients with oestrogen receptor (ER) positive and HER2 negative receptor disease were included in the study. ER-negative and HER2-positive disease was excluded, alongside patients who had chemotherapy before ANC. Of 102 patients, 58.8% (n=60) had no macrometastasis at ANC. On average, 2.76 lymph nodes were removed at SNB. A higher SNB ratio of positive to total nodes [OR 11.09 (CI 95% 2.33-52.72), P=0.002] had a significant association with positive nodes during ANC. SNB ratio less than or equal to 0.33 (1/3) had a specificity of 79.2% in identifying cases that later had a negative completion ANC, with a 95.8% specificity of no further upgrade of nodal staging. A low SNB ratio of less than 0.33 (1/3) has a high specificity in excluding the upgradation of nodal staging on completion of ANC, with a false-negative rate of less than 5%. This may be used to identify patients with a low risk of axillary metastasis, who can avoid ANC.

Cost-effectiveness of 2-[18F]FDG-PET/CT versus CE-CT for response monitoring in patients with metastatic breast cancer: a register-based comparative study

We evaluated the cost-effectiveness of 2-[18F]FDG-PET/CT compared to CE-CT for response monitoring in metastatic breast cancer (MBC) patients. The study included 300 biopsy-verified MBC patients treated at Odense University Hospital (Denmark). CE-CT was used in 144 patients, 83 patients underwent 2-[18F]FDG-PET/CT, and 73 patients received a combination of both. Hospital resource-based costs (2007–2019) were adjusted to the 2019 level. The incremental cost-effectiveness ratio (ICER) was calculated by comparing average costs per patient and gained survival with CE-CT. During a median follow-up of 33.0 months, patients in the 2-[18F]FDG-PET/CT group had more short admissions (median 6 vs. 2) and fewer overnight admissions (5 vs. 12) compared to the CE-CT group. The mean total cost per patient was €91,547 for CE-CT, €83,965 for 2-[18F]FDG-PET/CT, and €165,784 for the combined group. The ICER for 2-[18F]FDG-PET/CT compared to CE-CT was €-527/month, indicating gaining an extra month of survival at a lower cost (€527). 2-[18F]FDG-PET/CT was more cost-effective in patients with favorable prognostic factors (oligometastatic or estrogen receptor-positive disease), while CE-CT was more cost-effective in poor prognosis patients (liver/lung metastases or performance status ≥ 2 at baseline). In conclusion, our study suggests that 2-[18F]FDG-PET/CT is a cost-effective modality for response monitoring in metastatic breast cancer.

Characteristics and Treatment of Breast Cancer in Men: A 12-year Single-Institution Review

Background: Male breast cancer has a low incidence, hence there are few studies evaluating the disease, and no recent studies from Kenya. Objective: The objective of this study was to evaluate the clinical and pathological characteristics, and treatment of men diagnosed with breast cancer. Methods: This is a retrospective descriptive study, carried out at a tertiary hospital in Nairobi, Kenya, of men diagnosed with breast cancer between January 2009 and December 2021. Data on the clinicopathological characteristics, treatment, and outcome were collected. Standard descriptive statistics were used to describe the patient characteristics. Results: Seventeen male patients were diagnosed with breast cancer, representing 1.40% of all breast cancer patients. Four patients were excluded due to incomplete records. The median age at diagnosis was 68 years (range 28–83). The majority were African Bantu (n=11, 84.6%). Most patients presented with clinical T1 (n=10, 76.9%) and N0 (n=8, 61.5%) disease. Luminal A molecular subtype was the most common (n=8, 61.5%). All 11 patients who underwent operative management underwent modified radical mastectomy. Conclusion: The rate of male breast cancer was similar to the global rate. The majority of our patients presented with early breast cancer and estrogen receptor-positive disease. Treatment was primarily modified radical mastectomy followed by adjuvant systemic therapy.

Breast cancer mortality in 500 000 women with early invasive breast cancer diagnosed in England, 1993-2015: population based observational cohort study

ObjectivesTo describe long term breast cancer mortality among women with a diagnosis of breast cancer in the past and estimate absolute breast cancer mortality risks for groups of patients with...

Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

Anthracycline-taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline-taxane regimens. We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including MEDLINE, Embase, the Cochrane Library, and meeting abstracts to identify trials assessing anthracycline and taxane chemotherapy. Adjuvant or neoadjuvant trials were eligible if they began before Jan 1, 2012. Primary outcomes were breast cancer recurrence and cause-specific mortality. Log-rank analyses yielded first-event rate ratios (RRs) and CIs. 28 trials of taxane regimens with or without anthracycline were identified, of which 23 were deemed eligible, and 15 provided data on 18 103 women. Across all 15 trials that provided individual data, recurrence rates were 14% lower on average (RR 0·86, 95% CI 0·79-0·93; p=0·0004) with taxane regimens including anthracycline than those without. Non-breast cancer deaths were not increased but there was one additional acute myeloid leukaemia case per 700 women treated. The clearest reductions in recurrence were found when anthracycline was added concurrently to docetaxel plus cyclophosphamide versus the same dose of docetaxel plus cyclophosphamide (10-year recurrence risk 12·3% vs 21·0%; risk difference 8·7%, 95% CI 4·5-12·9; RR 0·58, 0·47-0·73; p<0·0001). 10-year breast cancer mortality in this group was reduced by 4·2% (0·4-8·1; p=0·0034). No significant reduction in recurrence risk was found for sequential schedules of taxane plus anthracycline when compared with docetaxel plus cyclophosphamide (RR 0·94, 0·83-1·06; p=0·30). For the analysis of anthracycline regimens with versus without taxane, 35 trials (n=52 976) provided individual patient data. Larger recurrence reductions were seen from adding taxane to anthracycline regimens when the cumulative dose of anthracycline was the same in each group (RR 0·87, 0·82-0·93; p<0·0001; n=11 167) than in trials with two-fold higher cumulative doses of non-taxane (mostly anthracycline) in the control group than in the taxane group (RR 0·96, 0·90-1·03; p=0·27; n=14 620). Direct comparisons between anthracycline and taxane regimens showed that a higher cumulative dose and more dose-intense schedules were more efficacious. The proportional reductions in recurrence for taxane plus anthracycline were similar in oestrogen receptor-positive and oestrogen receptor-negative disease, and did not differ by age, nodal status, or tumour size or grade. Anthracycline plus taxane regimens are most efficacious at reducing breast cancer recurrence and death. Regimens with higher cumulative doses of anthracycline plus taxane provide the greatest benefits, challenging the current trend in clinical practice and guidelines towards non-anthracycline chemotherapy, particularly shorter regimens, such as four cycles of docetaxel-cyclophosphamide. By bringing together data from almost all relevant trials, this meta-analysis provides a reliable evidence base to inform individual treatment decisions, clinical guidelines, and the design of future clinical trials. Cancer Research UK, UK Medical Research Council.

Abstract P3-05-51: Patients with low expression of BCL 2 experience more late recurrence than patients who do not, which neutralized the protective effect of low BCL2 expression in patients with estrogen receptor positive breast cancer

Abstract Background) BCL2 is a key factor for the regulation of cellular apoptosis and its overexpression inhibits apoptotic cell death and activates cellular proliferation, resulting tumor progression. Although BCL2 are expected to be associated with an adverse prognosis in breast cancer, previous studies have reported inconsistent results and some reported even favorable features. The aim of this study is to investigate what characteristics of BCL2 yield this discrepant result in patients with breast cancer. Materials and methods) Female patients with breast cancer who completed primary treatment against breast cancer between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. Clinocopathological characteristics including BCL2 expression were collected. Patients were categorized into two groups, BCL2 expression in more or less than 10% of tumor cells. Kaplan-Meier curves were generated to compare recurrence-free interval (RFI) and overall survival (OS). Result) The final cohort included 616 patients with a mean age of 54.79±11.2 (25-86) years. Patients with estrogen receptor positive breast cancer were more frequent in patients with tumor in which BCL2 was expressed in less than 10% of tumor cells (70.7% vs. 57.7%). Patients with tumor in which BCL2 was expressed in less than 10% of tumor cells showed better survival than their counterpart. Subgroup analysis according to the estrogen receptor and HER2 overexpression status was done. In patients with tumor in which HER2 was not overexpressed, patients with tumors in which BCL2 expressed less than 10% of tumor cells showed better survival(p=0.007). Survival difference maintained in patients with triple negative disease(p=0.010). However, in patients with estrogen receptor positive breast cancer, survival of two groups of patients with high and low BCL2 expression become not significant over time as late recurrence occurred (p=0.227). In contrast, patients with HER2 positive disease breast cancer showed worse prognosis than their counterpart when their tumor showed BCL2 expression in less than 10% of tumor cells. Conclusion) BCL2 overexpression showed different contribution to the patients’ survival according to the subtypes. Patients with HER2 overexpression showed better survival when BCL2 was overexpressed and patients with HER2 negative disease does not. First, similar survival was resulted from late recurrence in patients with estrogen receptor positive disease. Second, apoptotic capacity of tumor cells may not be major survival factor if tumor cells are exactly targeted. Citation Format: Hyang Suk Choi, Hany Hany Noh, In-Jeong Cho In-Jeong Cho, Seung Taek Lim, Jong-In Lee, Airi Han. Patients with low expression of BCL 2 experience more late recurrence than patients who do not, which neutralized the protective effect of low BCL2 expression in patients with estrogen receptor positive breast cancer [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 P3-05-51.

Abstract P5-02-27: Serum thymidine kinase activity as a prognostic marker in women with metastatic breast cancer treated with two different schedules of palbociclib plus second-line endocrine therapy within the CCTG MA38 trial

Abstract Background: Thymidine kinase-1 is a cell proliferation marker downstream of the CDK4/6 pathway, whose activity can be measured in serum to reflect tumor proliferation. The CDK4/6 inhibitor palbociclib (P) is approved for the treatment of patients (pts) with hormone receptor positive metastatic breast cancer (MBC) in first or second line endocrine-based treatment settings. Approximately 10-15% of pts exhibit de novo resistance to P, with circulating levels of thymidine kinase activity (TKa) previously shown as a potential marker of early treatment resistance. Therapeutic strategies to address primary resistance to P are currently lacking. Little is known of the clinical efficacy of alternative dosing schedules of P, and its effect on TKa. Here we report serum TKa measured at different timepoints from samples collected within the MA38 (NCT02630693) study. Methods: MA38 is an open label randomised Phase 2 trial comparing two different schedules of P plus second-line ET in pts with ER-positive, HER2-negative MBC. Pts were assigned to receive physician’s choice ET plus either standard P dosing (125mg daily for 21 days on a 28-day cycle), or 100mg daily continuously. Serum samples were collected at baseline (BL; n=135), at 12 weeks (W12; n=122) and 24 weeks (W24; n=95). TKa was measured with DiviTum®, a refined ELISA-based assay (lower limit of detection [LLOD] = 100 DuA). Kaplan-Meier method estimated BL, W12 and W24 (95% CI) median PFS (mPFS; from randomization until progression by RECIST criteria or death) and overall survival (OS; from randomization until death from any cause) in groups of patients defined by dichotomizing TKa as “high” or “low” at the median. Results: MA38 enrolled 180 pts from December 2015 and February 2017 across Canada. Median follow up was 19 months. Overall, the median age was 60, and 90% of pts were post-menopausal. All pts had estrogen receptor-positive disease, and 64% had visceral metastases. On study, 56% received fulvestrant with P, 34% aromatase inhibitor and 10% tamoxifen. TKa was successfully measured in 100% of samples. Median TKa (mTKa) at BL was 234 DuA (IQR 138.5 - 438). BL TKa was not associated with clinical or pathological characteristics. TKa was prognostic at BL with mPFS of 5.5 months (mo) in pts with high TKa vs 16.3 mo with low TKa (HR=2.43; 95% CI, 1.6-3.7; p&amp;lt; 0.001). Similar results were obtained employing other previously reported cut off values. At multivariate analysis, BL TKa was independent from other prognostic factors including age, ECOG status and presence of visceral metastases (adjusted HR= 2.34; 95%CI 1.5- 3.6; p &amp;lt; 0.001). In terms of OS, BL TKa was an independent prognostic factor (adjusted HR=2.0; 95% CI, 1.1-3.7; p=0.02). At 12 mo, OS rate was 68% in pts with high BL TKa vs 92% in low TKa. Both for PFS and OS, no interaction between BL TKa and study arm was observed. At W12 mTKa was 129.5 DuA (IQR 100 - 219.8) and below LLOD (IQR 100 - 180) at W24. At these timepoints, landmark analyses showed no significant difference in PFS according to TKa. However, at W12 high TKa was significantly associated with worse OS (HR 2.0; 95%CI 1.0- 4.0; p=0.03), with a similar trend at W24 (HR 2.5; 95%CI 0.9-6.4; p=0.06). Conclusions: Baseline TKa is a reliable prognostic marker of both PFS and OS in pts treated with P and ET, further substantiating previous data. Monitoring TKa during treatment may provide important clinical information. A significant relationship between TKa and assigned treatment arm was not observed, suggesting TKa is not influenced by P treatment dose or intensity. These data confirm the role of baseline TKa as a new marker for patient stratification, and supports further investigation for the assessment of the clinical utility of TKa as a monitoring biomarker in the advanced setting. Citation Format: Amelia McCartney, Chiara Biagioni, Bingshu Chen, Lois Shepherd, Karen Gelmon, Anil A. Joy, Wendy Parulekar, Mattias Bergqvist, Ilenia Migliaccio, Angela Leo, Matteo Benelli, Emanuela Risi, Erica Moretti, Luca Livraghi, Laura Biganzoli, Luca Malorni. Serum thymidine kinase activity as a prognostic marker in women with metastatic breast cancer treated with two different schedules of palbociclib plus second-line endocrine therapy within the CCTG MA38 trial [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 P5-02-27.

Abstract P1-07-09: Clinical and pathologic characteristics in early breast cancer Her2-low and high risk Oncotype DX RS

Abstract Background: Recent data suggest that HER2-low breast cancer (BC) may represent a distinct entity. Approximately 55-60% of BC are considered as Her2-low, of which 80% are Luminal-like tumors. Recent studies support potential clinic-pathological and molecular features differences between Estrogen Receptor (ER) positive HER2-low and ER positive Her2-0 disease. Among patients (pts) with high genomic risk (Oncotype DX RS) HER2-low expression was associated with a significant improvement in overall survival compared to Her2-0. The objective of our study is to compare disease characteristics and outcomes between HER2-low and Her2-0 in estrogen receptor (ER) positive, early (e) BC. (Murtai R et al. The Breast. 60(2021)62-69. Methods: A single center retrospective study of all pts. with ER positive, Her2 negative eBC, for whom Oncotype DX test was performed between 1/Nov/2012 and 14/Febr/2019. The pts were separated into HER2-low (immunohistochemistry (IHC) +1 or + 2 and in situ hybridization not amplified) or HER2-0. Clinic-pathological features included were: demographics, tumour size, nodal status, histologic grade, Her2 expression, ER and progesterone receptor (PR), Ki-67, presence of lymph-vascular (LV1) tumor cell invasion and Oncotype recurrence score (RS) result. Results: A total of 344 pts were screened, of whom 297 pts were included (Exclusion for: Her2 “negative” expression (45 pts); HER2 positive disease by IHC (1 pts); metastatic disease (1 pts)). The distribution of HER2-0 and HER2-low subgroups was 121 pts (41%) and 176 pts (59%). The pathological characteristics according to Her2 expression status are summarized in Table 1. Median age was 57 year (38-79), similar between both groups: Her2-0 58 yr (41-78) and 56 yr (38-79) in Her2 low. The postmenopausal status was 76 pts (62,8%) Her2-0 Vs 113 pts (64,2%) in Her2 low. 1 pts was male. Proliferation Index: Ki67% &amp;lt; 20 was: 65 pts (53,7%) Her2-0 Vs 86 pts (48,5%) in Her2 low; 65 pts (13,5%) had Lympho-vascular invasion in Her2 low; 115 pts (95%) were ER positive in Her2-0 Vs 157 pts (89,2%) in Her2 low; PR positive &amp;gt; 20 was 106 pts (87,6%) in Her2-0 Vs 137 (78,7%) in Her2 Low. The median follow-up was 72 month (SD+- 22,52). 5 pts had a recurrence: 4 pts were Her2 low (1 local and 3 distant metastasis) and 1 Her2-0 with distant metastasis. Most of the pts received adjuvant hormone therapy. There were no statistically significant differences between both groups owing to neither the clinic-pathologic features nor the recurrence score. It was not reached the mínimum number of events for a survival analysis. Conclusions: Our results show that HER2-low eBC pts have similar characteristics and survival rates compared to HER2-0 BC pts without significant differences. Table 1. Baseline pathological characteristics. Citation Format: Elena Galve, Fernando Pikabea-Diaz, Borja Lopez-de-San-Vicente-Hernandez, Covadonga Figaredo-Berjano, Jairo Legaspi-Folgueira, Maria Angeles Sala-Gonzalez, Juan Fernando Arango-Arteaga, Sara Fernandez-Ferrer, Pablo Leonardo Loaiza-Jaramillo, Pablo Casado-Cuesta, Marina Temino-Frances, Anne Bilbao-Penas, Purificacion Martinez-del-Prado. Clinical and pathologic characteristics in early breast cancer Her2-low and high risk Oncotype DX RS [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 P1-07-09.