Negative Progesterone Receptor Research Articles

Abstract PO2-01-11: Demographic, Lifestyle, and Clinical Factors Associated with Early vs. Late Recurrence among Women with Early-Stage Estrogen Receptor-Positive Breast Cancer in the Prospective Pathways Study

Abstract Background: Although women diagnosed with early-stage estrogen receptor (ER)-positive breast cancer generally have a favorable prognosis, they face a lingering risk of late recurrence that can occur years to decades after diagnosis. Relatively little is known about the demographic, lifestyle, or clinical factors associated with the risk of late recurrence, or whether the associations differ between early vs. late recurrence. Methods: We performed a comprehensive analysis of factors related to early vs. late recurrence in early-stage ER-positive breast cancer in the Pathways Study, an established prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California (KPNC) between 2006 and 2013. Recurrences were identified through monthly searches of the KPNC Cancer Registry, follow-up interviews with participants, and confirmation with electronic medical records. For this analysis, 2,473 women with stage I-IIB, ER-positive breast cancer were included, with ascertainment of recurrence and death through December 31, 2021. Univariate analysis and multivariable Cox regression models were used to examine the factors associated with early (< 5 years since diagnosis) and late (≥ 5 years since diagnosis) recurrence. Results: The median age of diagnosis was 57 (± 10) years, with 35% diagnosed before menopause. While 64% of patients self-reported as White, 16% identified as Asian, 6% Black, 12% Hispanic, and 2% other ethnicity. After a median 13.3 (range: 0.6-16.8) years of follow up, a total of 341 (13.8%) recurrences occurred, with 158 before and 181 at or after 5 years from diagnosis. Approximately a third of recurrences were local or regional and the other two thirds were distant. In univariate analysis, increasing stage and tumor grade were associated with higher risk of both early and late recurrence (p< 0.05). Progesterone receptor (PR) negativity was associated with only early (hazard ratio [HR]=1.49, 95% confidence interval [CI] 1.06-2.09) but not late recurrence (HR=0.90, 95% CI 0.63-1.28). In unadjusted models, receiving lumpectomy (vs. mastectomy), chemotherapy, radiation therapy, or endocrine therapy were associated with lower risk of both early and late recurrence. Among the demographic and lifestyle factors examined, postmenopausal status at diagnosis was associated with lower risk of early (HR=0.69, 95% CI 0.51-0.96) but not late recurrence (HR=1.00, 95% CI 0.73-1.36). No association was found with body mass index, socioeconomic measures (education, income, employment, marital status), smoking, alcohol intake, or physical activity assessed at the time close to diagnosis. Notably, minoritized racial/ethnic groups all had higher risk of early recurrence than White women (Asian: HR=1.76, 95% CI 1.16-2.66; Black: HR=2.33, 95% CI 1.38-3.93; Hispanic: HR=1.80, 95% CI 1.15-2.82), but no association was found with late recurrence (Asian: HR=0.99, 95% CI 0.65-1.51; Black: HR=0.80, 95% CI 0.41-1.58; Hispanic: HR=0.80, 95% CI 0.48-1.33). In multivariable Cox models adjusted for age, cancer stage, grade, PR status, surgery, radiation therapy, chemotherapy, and endocrine therapy, the trend of higher risk of early recurrence among minoritized racial/ethnic groups remained, although the association remained significant only in Black women (HR=1.89, 95% CI 1.08-3.31). Conclusion: Most histopathological features and cancer treatment modality had similar impact on early vs. late recurrence among women with early-stage ER-positive breast cancer, although PR negativity might be an adverse risk factor for early recurrence only. The findings of higher risk of early but not late recurrence among Asian, Black, and Hispanic relative to White women provide some novel data on the racial/ethnic disparities of prognosis for ER-positive breast cancer and may warrant further investigation. Citation Format: Alfredo Chua, Haiyang Sheng, Shipra Gandhi, Marilyn Kwan, Isaac Ergas, Janise Roh, Cecile Laurant, Thaer Khoury, Scarlett Gomez, Christine Ambrosone, Lawrence Kushi, Song Yao. Demographic, Lifestyle, and Clinical Factors Associated with Early vs. Late Recurrence among Women with Early-Stage Estrogen Receptor-Positive Breast Cancer in the Prospective Pathways 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 PO2-01-11.

Abstract PO3-01-12: Clinicopathologic Factors affecting response in patients with Estrogen receptor-positive and Human Epidermal Growth Factor Receptor-negative breast cancer receiving neoadjuvant chemotherapy

Abstract Background: The evolution of Neoadjuvant chemotherapy(NAC) regimen has enabled the down-staging of locally advanced breast cancer, allowing patients to undergo breast conserving surgery. NAC is known to be effective in triple-negative breast cancer (TNBC) and HER2-positive breast cancer. However, the role of NAC in hormone receptor-positive and HER2-negative (HR+HER2-) breast cancer patients remains unclear. In this study, we aimed to explore the utility of NAC for estrogen receptor-positive and HER2-negative (ER+HER2-) breast cancer patients. Methods: Clinical data were collected from 120 patients who were diagnosed with estrogen receptor (ER)-positive and HER2-negative breast cancer and received neoadjuvant chemotherapy between July, 2017 and April, 2023 at Seoul St Mary’s Hospital (Seoul, Korea). We analyzed the factors that affect clinical response subgroups, including pathologic complete response (pCR), partial response (PR), stable disease(SD), and progressive disease (PD), following neoadjuvant chemotherapy. The median follow-up period was 17 months. < Results: Among 120 patients after NAC, 5.8% achieved pCR, while 67.5% had a partial response. The median age at the time of surgery was 55 years at pCR group, 49 years at PR group, 47 years at SD group, and 49 years at PD group. Although the age of patients achieving pathological complete response was higher, this differences was not statistically significant. Patients achieving pCR had a higher incidence of progesterone receptor (PR) negativity (pCR 71.4% vs PR 30.9%, p=0.011) and higher levels of Ki-67 expression than those who did not achieve pCR (71.7% vs 35.6%, p=0.003). Also, there was no significant difference in Androgen receptor (AR) and HER-2 expression between the groups. Tumor size was also significantly associated with clinical response (p=0.003). However, no differences in clinical response was observed between patients with lymph node metastasis (p=0.221). Our analysis of 107 patients who were clinically N positive before NAC showed that the Ki-67 index level was the only factor found to affect nodal pCR. In addition, in the non-pCR group, patients with a Ki-67 index of less than 20% after neoadjuvant had a significantly better disease-free survival (5yr DFS, 79.8% vs 65.9%, p=0.039) Conclusion: Our analysis revealed that patients with higher levels of Ki-67 and lower level of PR expression were more likely to achieve pCR or PR. Also, decrease in Ki-67 index was confirmed to be an important prognostic factor of ER+ HER2- breast cancer. A combination of clinical and molecular factors, such as tumor size, progesterone receptor expression, and Ki-67 expression, can be used to optimize treatment plans and improve outcomes for the patient population. Citation Format: Jin Ah Lee, Young Joo Lee, Dooreh Kim, Chang Ik Yoon, Woo-Chan Park, Soo Youn Bae. Clinicopathologic Factors affecting response in patients with Estrogen receptor-positive and Human Epidermal Growth Factor Receptor-negative breast cancer receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-12.

Triple-Negative Breast Cancer Treatment Advancements: A Review of Evolving Strategies

Women around the world are most frequently afflicted with breast cancer, and it is one of the most frequent causes of cancer death in females. Breast cancer is usually classified according to biomarker status, triple‐negative breast cancer (TNBC) represents a distinct subtype characterized by immunohistochemical findings that denote negativity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (Her-2) on cancer tissue. It is more common in younger women than in other subtypes. As an invasive breast cancer subtype with a unique drug-resistant phenotype and metastatic burden, it has limited treatment options, and patients have a poor prognosis with high rates of local, distant recurrence and mortality, and there is still a lack of standardized treatment protocols for TNBC. In this review, we delve into the current treatment strategies for TNBC and explore the potential for new approaches and targets in the future. This trial is registered with NCT03997123.

Vascular Endothelial Growth Factor Expression by Immunohistochemistry as a Possible Indicator of Prognosis in Invasive Breast Carcinoma of No Special Type

Context: Angiogenesis, the formation of new blood vessels from preexisting vascular network, is essential for tumor growth and spread. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor. Aims: To assess the expression of VEGF in invasive carcinoma of no special type and its correlation with all the known prognostic factors of breast carcinoma. Settings and Design: Descriptive. Materials and Methods: Mastectomy specimens were studied noting the clinical details. The formalin-fixed tissues were subjected to routine processing and hematoxylin and eosin sections and studied extensively for all the histological prognostic factors. Representative sections from each case with the tumor were subjected to immunohistochemistry (IHC) staining with VEGF, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) antibodies. Statistical Analysis Used: Descriptive statistics, Chi-square tests, contingency table analysis using SPSS for Windows. Results: One hundred and twelve cases of invasive carcinoma of special type were studied to evaluate various clinicopathological parameters. The association of VEGF with clinicopathological parameters and all the known prognostic factors was studied to note its significance. VEGF overexpression was observed in 69% of the cases. It was noted that larger tumor size, higher histological grade, lymphovascular invasion, nodal involvement, tumor necrosis, high microvessel density, ER negativity, PR negativity, and HER2/neu positivity had a significant statistical association with VEGF overexpression. Conclusions: We conclude that incorporating VEGF as a biomarker along with the known factors into a prognostic index will not only help predict clinical outcome more accurately, but also determines the patient who can be benefited with combinational therapy including anti-VEGF factors.

Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan

BackgroundBreast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation.MethodologyA cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years.ResultsOne hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40–50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases.ConclusionIn our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

Primary Rectal Perineurioma: A Rare Incidental Finding

Abstract Perineurioma is a rare benign peripheral nerve sheath tumor which can occur intraneurally or uncommonly in the extraneural soft tissues. The majority of the perineuriomas of the gastrointestinal tract occur distal to the splenic flexure as polypoid pedunculated or sessile lesions. Lesions are often discovered incidentally during routine colonoscopy for cancer screening. Diagnosis is mainly histological with the majority of the cases showing mucosal/submucosal bland spindle cell proliferation with expression of perineurial markers. We report a rare case of rectal perineurioma in a 42-year-old female who presented with the complaint of intermittent episodes of painless rectal bleed associated with defecation. A pedunculated polypoid lesion in the rectum measuring 12 mm in greatest dimension was seen on colonoscopy. The patient underwent endoscopic mucosal resection of the mass. Microscopically, the lesion showed proliferation of spindle cells with oval-to-spindle nuclei, bland chromatin, and moderate amount of pale to eosinophilic cytoplasm with indistinct cell borders. Overlying mucosa showed hyperplastic crypt epithelium. Spindle cells were positive for epithelial membrane antigen and CD 34 and negative for S100, with low Ki-67 marked cycling cell population (<1.0%) and negative Progesterone receptor (PR) and CD 117, these features confirming the diagnosis of perineurioma.

Breast Cancer Clinicopathology based on Neutrophil Levels at Adam Malik Hospital Medan in 2018-2021

Introduction: Breast cancer is the most frequently diagnosed cancer in the world. Breast cancer occurs due to abnormal cell growth in breast tissue so that it becomes malignant. In Indonesia, breast cancer is the most common cancer in women. That way, many markers are needed as prognostic and predictive of breast cancer. One of the prognostic factors for breast cancer is neutrophil levels combined with clinicopathological factors. Objective: Knowing the clinicopathology of breast cancer based on neutrophil levels at the Haji Adam Malik Medan General Hospital in 2018-2021. Methods: The research design is observational with a descriptive method and calculated using the Lemeshow formula. Results: Majority aged 40-49 years (39.6%), high school (44.8%), housewives (67.7%), no family history (97.9%), tumor grade II (38.5%) %), Tumor Infiltrating Lymphocytes (TILs) severe (47.9 %), mitotic score 1 (38.5 %), metastatic positive lymph node status (87.5 %), tumor size T1 (36.5 %), The number of positive and negative Estrogen Receptors is the same (50.0%), Progesterone Receptor is negative (56.3%), HER2 is 1+ (60.4%), Ki-67 is positive (84 .4 %), positive angioinvasion (63.5 %), Invasive Ductal Carcinoma (90.6 %), high neutrophil levels (77.1 %). Conclusion: High levels of neutrophils tend to result in severe Tumor Infiltrating Lymphocytes (TILs) which will increase tumor growth, occurrence of metastases, increased positive angioinvasion, negative Estrogen Receptor status, negative Progesterone Receptor status, HER2 1+ status, positive Ki-67 status.

Efficacy, safety, and prognosis prediction in patients treated with ribociclib in combination with letrozole: Final results of phase 3b RIBECCA study in hormone receptor positive, human epidermal growth factor receptor-2 negative, locally advanced or metastatic breast cancer

BackgroundIn MONALEESA-2, addition of ribociclib to letrozole resulted in significantly longer progression-free survival (PFS) in postmenopausal women with HR+HER2− advanced breast cancer (ABC). RIBociclib for the treatment of advanCed breast CAncer (RIBECCA) study investigated ribociclib plus letrozole in a patient population reflecting routine clinical practice. Patients and methodsIn this multicenter, open-label, single-arm, phase 3b study, patients with HR+HER2− ABC not amenable to curative therapy and ECOG performance status ≤ 2 received ribociclib plus letrozole (cohort A: postmenopausal women and men in first-line; cohort B: pre-/perimenopausal women in first-line [B1], patients pretreated for advanced disease [B2]). The primary endpoint was clinical benefit rate (CBR) by week 24; secondary endpoints included overall response rate (ORR), PFS, overall survival (OS), and safety. Association of patient and tumor characteristics with PFS was analyzed by multivariable Cox regression analysis. ResultsOverall, 487 patients were evaluable for efficacy, 502 for safety. By week 24, CBR was 60.8 % (95 % CI, 56.3–65.1), ORR was 19.3 % (95 % CI, 15.9–23.1). Median PFS was 21.8 months (95 % CI, 13.9–25.3) in first-line postmenopausal patients and 11.0 months (95 % CI, 8.2–16.4) in premenopausal and pretreated patients. Median OS was not reached. Higher baseline ECOG performance status, higher histological grade, and negative progesterone receptor status showed an unfavorable effect on PFS. Most common adverse events were neutropenia (50.0 %), nausea (42.0 %), and fatigue (39.2 %). ConclusionIn this broad population of patients with HR+HER2− ABC, efficacy and safety results of ribociclib plus letrozole were similar to those observed in pivotal trials.

Complete pathological response in patients with HER2 positive breast cancer treated with neoadjuvant therapy in Colombia

Breast cancer is the most common type of cancer and the leading cause of death by cancer in women in Colombia. Approximately 15 to 20% of breast cancers overexpress HER2. To analyze the relationship between multiple clinical and histological variables and pathological complete response in patients with HER2-positive breast cancer undergoing neoadjuvant therapy in a specialized cancer center in Colombia. We performed a retrospective analysis of non-metastatic HER2-positive breast cancer patients who received neoadjuvant therapy between 2007 and 2020 at the Instituto de Cancerología Las Americas Auna (Medellín, Colombia). Assessed parameters were tumor grade, proliferation index, estrogen receptor, progesterone receptor, HER2 status, type of neoadjuvant therapy, pathologic complete response rates, and overall survival. Variables associated with low pathologic complete response rates were tumor grades 1-2 (OR = 0.55; 95% CI = 0.37-0.81; p = 0.03), estrogen receptor positivity (OR =0.65; 95%; CI = 0.43-0.97; p=0.04), and progesterone receptor positivity (OR = 0.44; 95% CI = 0.29-0.65; p = 0.0001). HER2 strong positivity (score 3+) was associated with high pathological complete response rates (OR = 3.3; 95% CI = 1.3-8.35; p=0.013). Five-year overall survival was 91.5% (95% CI = 82.6-95.9) in patients with pathological complete response and 73.6% (95% CI = 66.4-79.6) in patients who did not achieve pathological complete response (p = 0.001). Additionally, the pathological complete response rate was three times higher in patients receiving combined neoadjuvant chemotherapy with anti-HER2 therapy than in those with chemotherapy alone (48% versus 16%). In patients with HER2-positive breast cancer, tumor grade 3, estrogen receptor negativity, progesterone receptor negativity, strong HER2 positivity (score 3+), and the use of the neoadjuvant trastuzumab are associated with higher pathological complete response rates.

Survival Analysis of Breast Cancer in Patients with HER2/neu+, ER-, PR-: a Retrospective Cohort Study

Aim: We aimed to study the characteristics of the breast cancer patients with positive HER2/neu+, ER- and PR- receptors. Methods: 119 patients with breast cancer were included in this retrospective cohort study from 2006 to 2016. The overall and disease-free survival were evaluated. Results: Most prevalent type of tumor was IDC, grade III cancer and stage II. Recurrence/metastasis occurred in 18.49%. Most common sites of metastasis were lungs and liver. Total mortality rate was 10.92%. Overall and disease-free survival times were 40.04 and 22.29 months, respectively. The median survival time was about 118 months. Conclusion: Breast cancers with positive HER2/neu and negative estrogen and progesterone receptors had low overall and disease-free survival rates compared with ER+/PR+/HER2- tumors.

The prognostic significance of skin involvement in breast cancer patients with chest wall recurrence

Purpose To assess the prognostic significance of skin involvement in breast cancer patients with chest wall recurrence (CWR). Methods We retrospectively analyzed the clinicopathological data of breast cancer patients with CWR who were diagnosed pathologically between January 2000 and April 2020. Disease-free survival (DFS) was the time from radical resection for CWR to disease recurrence. Progression-free survival (PFS) was defined as the time from the diagnosis of locally unresectable CWR to the first sign of disease progression. Persistent chest wall progression was defined as three consecutive chest wall progressions with no distant organ involvement. Results A total of 476 patients with CWR were included in this study. Skin involvement was confirmed in 345 patients. Skin involvement was significantly correlated with a high T stage (p = 0.003), more positive nodes at initial examination (p < 0.001) and lymphovascular invasion (p < 0.001). Kaplan–Meier analysis showed that skin involvement was a predictor of shorter DFS (p < 0.001), including both local disease progression (p < 0.001) and distant disease progression (p = 0.022). Multivariate analysis showed that skin involvement was an independent biomarker for DFS (p = 0.043). Patients with skin involvement were more likely to experience persistent chest wall progression (p = 0.040). After eliminating the potential deviation caused by an insufficient follow-up time, persistent chest wall progression was more likely to be associated with a high N stage (p = 0.002), negative progesterone receptor (PR; p = 0.001) and positive human epidermal growth factor receptor 2 (HER2; p = 0.046) of the primary site, and negative oestrogen receptor (ER; p = 0.027) and PR (p = 0.013) of the chest wall lesion and skin involvement (p = 0.020). Conclusion Skin involvement was a predictor of poor disease control in patients with CWR and was closely related to persistent chest wall progression. We stratified the prognosis of individualized treatment for breast cancer patients with CWR to provide new insights into the biological behaviours of the disease.

Progesterone receptor expression and prediction of benefits of adjuvant radiotherapy in de novo atypical meningiomas after gross-total resection.

Benefits of adjuvant radiotherapy (ART) after gross-total resection (GTR) of de novo atypical meningiomas (AMs) are controversial, and factors predictive of radiotherapy benefits in patients with de novo AMs after GTR are unknown. The authors aimed to evaluate the benefits of ART and explore potential factors sensitizing AMs to ART. A total of 231 consecutive patients who were pathologically diagnosed with de novo AMs and treated with GTR (Simpson class I-III resections) from 2010 to 2018 were enrolled in the study. Clinicopathological and prognostic information was collected and analyzed. Univariate and multivariate Cox analyses were used to evaluate prognostic predictors and compare the response to radiotherapy. Propensity score matching (PSM) was used to balance the confounding bias in subgroups. A total of 138 patients (59.74%) received ART. Progesterone receptor (PR) expression was positive in 157 patients (67.97%). During the mean follow-up period of 76.25 months, 65 patients (28.14%) experienced recurrence and 38 (16.45%) died of tumor progression. For disease-specific survival (DSS), ART was a better prognostic factor via univariate (p = 0.003) and multivariate (p = 0.025) analyses. For progression-free survival (PFS), univariate Cox analysis showed that ART improved PFS (p = 0.013), but multivariate analysis did not (p = 0.068). Positive PR expression (p = 0.019), age 53.5 years or younger (p = 0.012), and Ki-67 7.5% or lower (p = 0.025) were independent prognostic predictors for better PFS. In the subcohort analysis, the beneficial impact of ART was observed in the PR-negative cohort (p = 0.002) but not in the PR-positive cohort (p = 0.86). The heterogeneity analysis demonstrated that the PR-negative cohort was more sensitive to ART than the PR-positive cohort (p = 0.036). ART was not found to be associated with better PFS in younger patients (≤ 53.5 years, p = 0.14), older patients (> 53.5 years, p = 0.085), those with a Ki-67 index ≤ 7.5% (p = 0.068), or those with a Ki-67 > 7.5% (p = 0.13). The contrasting effects of ART in the PR-negative versus PR-positive cohorts remained true even after PSM, confirming that PR-negative, but not PR-positive, de novo AMs benefited from ART after GTR. ART was an independent prognostic factor for DSS of patients with de novo AMs treated with GTR (p = 0.025), but not for PFS (p = 0.068). Negative PR expression was a radiosensitive biomarker on PFS for de novo AM patients after GTR.

Circulating tumor cells in patients with hormone receptor-positive, HER2-negative metastatic breast cancer receiving palbociclib with fulvestrant after progression on palbociclib with an aromatase inhibitor.

e13018 Background: High levels of circulating tumor cells (CTCs) at initiation of therapy in patients with metastatic breast cancer (MBC) are associated with worse prognosis. In patients with hormone receptor–positive (HR+), HER2-negative MBC, the benefit of maintaining CDK4/6 inhibitor (CDK4/6i) after progression on first-line therapy with endocrine therapy and CDK4/6i is not fully defined. To study the relationship between CTCs, tumor characteristics, and clinical outcomes, we enumerated CTC dynamics in patients with HR+ HER2- MBC enrolled on a phase II, multi-center, open-label interventional trial of palbociclib and fulvestrant after disease progression on prior palbociclib with an aromatase inhibitor (NCT02738866). Methods: Blood samples from study participants were collected at baseline (pretreatment), cycle 2 (C2, 8 weeks after initiation of fulvestrant and palbociclib), and at disease progression. Using a previously analytically validated assay (CellSearch), CTCs were enumerated. Progression-free survival (PFS) was estimated using the Kaplan Meier method. The relationship between CTC count at baseline (&lt; 5, &gt;5/7.5 ml Whole Blood (WB)) and PFS was analyzed using Cox proportional hazards regression. The association between PFS and CTC count among patients with baseline CTC ≥5 was estimated with a Cox proportional hazards model, adjusting for age, race, and progesterone receptor (PgR). Results: Between May 2017 and September 2022, baseline samples were collected from 52 of 60 trial participants enrolled at 5 centers in the United States, mean age 55 years (SD 14). Baseline CTC counts were &lt;5 in 30/52 (58%) and &gt;5 in 22/52 (42%) of participants. Among participants at baseline, only tissue PgR negativity was associated with higher likelihood of having elevated CTCs &gt;5 (p = 0.04). Association of CTCs &gt;5 and select patient and tumor characteristics is shown in Table 1. There was no statistically significant association between continuously measured CTC and PFS among those with elevated CTCs at baseline. Median duration of therapy among the entire 52 participant cohort was 4 months. Median PFS in participants with baseline CTC &lt;5 vs &gt;5/7.5 ml WB was 7.83 (95% CI [5.37, 12.60]) and 2.83 (95% CI [1.77, 4.73]) months, respectively (HR): 2.10, 95% CI [1.15, 3.82], p = 0.01). Conclusions: Baseline CTCs &gt;5/7.5 ml WB conferred a 2-fold increased risk of disease progression. Tissue PgR negativity was associated with baseline CTCs &gt;5. These data can be used to inform new studies in which baseline and early change in CTCs may inform second line treatment decisions in women with HR+, HER2- MBC. [Table: see text]

142P The predictive value of progesterone receptor expression on pCR following neoadjuvant chemotherapy in breast cancer

The efficacy of neoadjuvant chemotherapy (NAC), as measured by the pathological complete response (pCR), varies between molecular subtypes in breast cancer (BC). Oestrogen receptor (ER)-positive, human epidermal growth factor 2 receptor (HER2)-negative patients tend to have lower pCR rates. The transcription of the progesterone receptor (PR) is dependent on the ER therefore PR negativity may suggest an erroneous oestrogen signalling pathway rendering resistance to endocrine therapy. PR- tumours tend to be more aggressive but more chemosensitive. This study aimed to determine if PR status, no longer routinely tested in ER+ BC in the UK, can identify which ER+/HER2- patients will achieve pCR. This would enable more appropriate selection of patients for NAC. Patients undergoing NAC at the Royal Victoria Infirmary, Newcastle, between 2013 and 2021 were identified and their clinicopathological features were collated in a retrospective dataset. PR status was ascertained with standard immunohistochemistry. The PR score was correlated with the pCR rate. Overall survival (OS) and disease-free survival (DFS) were calculated against pCR. 244 patients were included in the analysis (78 triple-negative BC (TNBC); 25 ER+/HER2-; 141 HER2+). In the ER+/HER2- group, PR- patients achieved higher rates of pCR compared to PR+ patients (31% and 9%; χ2; p=0.327). The pCR rate in the ER+/HER2-/PR- group was not statistically different to that of TNBC (31% and 29%; Fisher’s exact test; p=1.000). In the ER+/HER2+ group, PR- patients achieved higher rates of pCR than PR+ patients (23% and 4%; χ2; p=0.090). The breast pCR rate in the ER+/HER2+ group was statistically different (52% and 24%; χ2; p = 0.015) when comparing PR- and PR+ patients. Oncological outcomes of patients that achieved pCR were significantly improved (DFS p = 0.005; OS p = 0.032). PR- patients achieved higher rates of pCR in both ER+/HER2- and ER+/HER2+ subtypes. ER+/HER2-/PR- tumours may behave more like TNBCs than hormone-positive BCs and require more aggressive chemotherapeutic strategies. PR status has value in determining which ER+ patients might benefit from NAC with improved oncological outcomes.

71P MicroRNA (miRNA) a putative biomarker to better define the molecular apocrine breast cancer (MABC) subtype

Breast cancer (BC), is a heterogeneous disease, divided into molecular subtypes based on gene expression and clinical outcomes. MABC is a poorly diagnosed subtype, characterized by estrogen (ER), progesterone receptor (PR) negativity, and HER-2-amplification in most cases; yet it overexpresses androgen receptor (AR) and activates its pathway. Its improper diagnosis demands the adoption of complementary tools to refine classification; miRNA, key players in regulating cell behavior, AR, and tumorigenic processes of BC hold promise in defining and studying the behavior of MABC. 539 breast cancer microarray data were downloaded from The Cancer Genome Atlas (TCGA-BRCA). Cases with available miRNA data were retained and classified using citbcmst R package (PMID: 30289602). Differential expression analysis identified deregulated miRNAs using DEseq2. A validation set of 131 ER-neg samples was constituted and MABC tumors were characterized apart of triple-negative (TN)BC by the previously described molecular signature (AR, FOXA1 and AR-related genes, PMID: 23663520) on fresh tissue sections. Using miRCURY LNATM miRNA PCR assay, miRNA profiling was done for a panel of 6 differentially expressed miRNAs. Finally, expression of in silico predicted target genes of these miRNAs was assessed by RT-qPCR in MABC and TNBC cell lines after transfection with miRNA mimics. TCGA data analysis indicated MABC as a separate entity based on gene signature. MiRNA-seq data analysis depicted a set of 6 significantly deregulated miRNA with absolute value of log2 fold change> 1 and P-adjusted value <0.05 between MABC and TNBC. We validated on 78 MABC (27 HER2-/ 51 HER2+), and 53 TN samples, by miRNA profiling, significant upregulation of miR-2115-3p and miR-187-3p in MABC compared to TNBC. Preliminary data, showed that the overexpression of these miRNAs significantly downregulates in silico predicted target genes (FGF2, HMGCS1, and ADAM12) implicated in carcinogenesis differently in each of the models used. MABC has a unique signature of miRNA compared to TNBC. The identified miRNAs regulate a set of genes implicated in tumorigenic processes and can potentially serve as biomarkers to effectively diagnose, prognose and treat MABC

493 Triple negative status and progesterone receptor conversion between primary breast cancer and skin metastasis render worst survival among patients with stage 4 breast cancers

493 Triple negative status and progesterone receptor conversion between primary breast cancer and skin metastasis render worst survival among patients with stage 4 breast cancers

Incidence, Clinicopathologic Features, HER2 Fluorescence In Situ Hybridization Profile, and Oncotype DX Results of Human Epidermal Growth Factor Receptor 2-Low Breast Cancers: Experience From a Single Academic Center

Human epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by an immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization, is emerging as a predictive marker for the use of the antibody-drug conjugate. To understand how this category differs from HER2-zero cases, we investigated clinicopathological characteristics and HER2 fluorescence in situ hybridization results in a large cohort of 1309 continuous HER2-negative invasive breast carcinomas from 2018 to 2021 evaluated by the Food and Drug Administration-approved HER2 IHC test. Additionally, we compared Oncotype DX recurrence scores and HER2 mRNA expression between HER-low and HER2-zero cases in a separate cohort of 438 estrogen receptor-positive (ER+) early-stage breast carcinoma cases from 2014 to 2016. Based on the cohort from 2018 to 2021, the incidence of HER2-low breast cancers was approximately 54%. HER2-low cases had less frequent grade 3 morphology, less frequent triple-negative results, ER and progesterone receptor negativity, and a higher mean HER2 copy number and HER2/CEP17 ratio than HER2-zero cases (P < .0001). Among ER+ cases, HER2-low cases showed significantly less frequent Nottingham grade 3 tumors. In the cohort from 2014 to 2016, HER2-low cases showed significantly higher ER+ percentages, fewer progesterone receptor-negative cases, lower Oncotype DX recurrence scores, and higher HER2 mRNA expression scores than HER2-zero cases. In summary, this is the first study, to our knowledge, using a large cohort of continuous cases evaluated by the Food and Drug Administration-approved HER2 IHC companion diagnostic test for HER2-low expression and HER2 fluorescence in situ hybridization profile in a real-world setting. Although HER2-low cases showed a higher HER2 copy number, ratio, and mRNA level than HER2-zero cases statistically, such small differences are unlikely to be biologically or clinically meaningful. However, our study suggests that HER2-low/ER+ early-stage breast carcinoma may represent a less aggressive group of breast carcinoma, given its association with a lower Nottingham grade and Oncotype DX recurrence score.

Immunohistochemical expression of CD155 in invasive female breast carcinoma and its correlation with tumor infiltrating natural killer cells

BackgroundCD155 is an immune checkpoint protein that interacts with ligands on natural killer cells to regulate the tumor associated immunity. CD155 overexpression has been detected in many human cancer types. CD155 and its pathways are promising tumor immunotherapy targets. We aimed to evaluate the immunohistochemical expression of CD155 in invasive breast carcinomas and to correlate such expression with the pathological parameters of the tumors and also with natural killer - tumor infiltrating lymphocytes (NK-TILs) density in breast carcinomas tissue as highlighted by CD56 immunostaining. This study included 78 cases of breast carcinomas. Immunohistochemistry was performed using antibodies against CD155 which was detected on the tumor cells and CD56 as a marker for stromal NK cells.ResultsCD155 expression by the tumor cells was detected in 30.8% of the cases and correlated significantly with advanced prognostic stage, Estrogen receptor (ER) and Progesterone receptor (PR) negativity, high Ki-67 index and Human epidermal receptor 2 (HER2) enriched molecular subtype. High stromal TILs CD56 expression was detected in 28.2% of the cases and correlated significantly with high histologic grade, PR negativity, HER2 neu over-expression, high Ki-67 index, high stromal TILs and more aggressive molecular subtypes; triple negative breast cancer, HER2 enriched and Luminal B-HER2 positive. Finally, statistically significant direct correlation was detected between Tumor cells CD155 expression and high TILs CD56 expression.ConclusionsOur results support tumor cell CD155 expression and TILs CD56 expression in breast cancers that are high grade, TILs rich and hormone receptors negative, highlighting those cases as possible candidates for CD155 targeted therapy.

Abstract P2-11-02: BIOMARKERS RELATED TO SURVIVAL BENEFIT IN THE TREATMENT OF METASTATIC LUMINAL BREAST CANCER (mBC) WITH CYCLIN 4/6 INHIBITORS (CDK 4/6i) PLUS ENDOCRINE THERAPY (ET)

Abstract Treatment with CDK4/6i plus ET is the standard treatment for mBC with a significantly better progression free survival (PFS) and a long treatment duration response, although there’s finally a progression. The expression of cyclin E and progesterone receptor had been related to survival, so analyzing of these potential biomarkers could help to select their effect in patients with a long treatment duration (&amp;gt; 20 months). We evaluate 68 mBC treated with CDK4/6I plus ET as a clinical practice in a single institution. Median age was 68 years, 27(39,7%) patients had de novo metastatic disease, 17 (25%) progressed during ET adjuvant, and 24 (35,3%) progressed after 5 years of ET. Forty-eight patients (70%) received CDK4/6I plus ET in first line and visceral disease was present in 40% of patients. The median expression by histoscore with immunohistochemistry of cyclin E (CycE) was 75,3 (4-97) and progesterone receptor (PR) 121. Median PFS was 16 months (8,3- 23,6) with 45 events, 25 months in patients treated in first line and 12 months in second line (p: 0,0001). We analyzed 59 patients who had already completed CDK4/6I plus ET or had achieved a PFS more than 20 months, 40 (69%) in first line and 18 (31%) in second line. We summarized the related of expression of PR, CycE and this combination with PFS more than 20 month. CONCLUSION: Treatment with CDK4/6i plus ET achieved long treatment duration in patients with low expression of cyclin E (OR 3,1 p:0,045), positive progesterone receptor (OR 3,89 p: 0023) and specially in patients with positive progesterone receptor and low expression of cyclin E (OR 7,22 p:0,016). Patients with negative progesterone receptor and high expression of cyclin E had a poor prognosis with a median disease-free survival of 6 months (2.8 – 9.2), so these patients required other treatment approaches to improve their outcomes. Table Citation Format: Serafin Morales Murillo, Ariadna Gasol Cudós, Noemí Tuset Der-Abrain, Izaskun Urdanibia, Alvaro Rodriguez Galindo, Ana Velasco Sánchez, Felip Vilardell Villellas, Douglas Sánchez Guzmán, Carles Canosa Morales, Jordi Melé Olivé, Laura Arbones Cid. BIOMARKERS RELATED TO SURVIVAL BENEFIT IN THE TREATMENT OF METASTATIC LUMINAL BREAST CANCER (mBC) WITH CYCLIN 4/6 INHIBITORS (CDK 4/6i) PLUS ENDOCRINE THERAPY (ET) [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 P2-11-02.

Predicting response to neoadjuvant therapy with glucose transporter-1 in breast cancer.

Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated. A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy.