ER-positive Research Articles

Nodal Response and Survival After Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive Breast Cancer: 20-Year Experience from a Single Institution.

Axillary response to neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive breast cancer (HR+ BC) is not well-described. This study was designed to characterize nodal response after NET. Patients receiving NET followed by curative intent surgery at a comprehensive cancer center from 1998 to 2022 in a prospectively collected registry were included. Patients with distant metastasis were excluded. Primary outcome was nodal pathologic complete response (pCR). Downstaging was defined as post-NET decrease in category. We included 123 patients; the majority were cT2 (n = 59) or cT3 (n = 35), and cN0 (n = 81). Median age was 70.0 years (interquartile range 62.1-76.0). Forty-two patients (34.1%) were clinically node-positive. After NET, 73 (59.8%) underwent breast-conserving surgery. All patients underwent sentinel lymph node biopsy, and 12 (9.8%) underwent completion axillary lymph node dissection. In-breast downstaging was achieved in 51 (41.5%) patients, 1 (0.8%) had breast pCR, and 14 (11.4%) had breast upstaging. Axillary downstaging was achieved in 10 (23.8%), 6 patients (14.3%) had nodal pCR, and 14 (33.3%) had axillary upstaging. At 10-year follow-up, local recurrence was 1% and distant recurrence was 14%, while disease-free survival was 82%. After adjusting for demographic and clinical factors, age was the only characteristic associated with mortality (hazard ratio 1.07, 95% confidence interval 1.01-1.13). In HR+ BC treated with NET, long-term disease-free survival is good, although nodal pCR is uncommon for cN+ patients. Future studies are needed to elucidate optimal neoadjuvant systemic therapy and to delineate oncologically safe strategies to deescalate axillary management for residual microscopic disease.

Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway

CDK4/6 inhibitors combined with endocrine therapy prolonged survival in hormone receptor (HR)-positive and HER2-negative advanced breast cancer. We investigated whether CDK4/6 inhibitors enhance radiosensitivity and their underlying mechanisms of this subtype of breast cancer. In vitro and in vivo experiments were conducted using two HR-positive and HER2-negative breast cancer cell lines (MCF-7 and T-47D), CDK4/6 inhibitors (ribociclib and palbociclib) and radiotherapy (RT) to assess the biological functions and mechanisms. The radiation-enhancing effect was assessed using clonogenic assays; γH2AX and 53BP1 levels were assessed by immunofluorescence to evaluate DNA damage. The levels of phospho (p)-ERK, c-Myc, and DNA-double strand break (DSB)-related molecules, p-DNA-PKcs, Rad51, and p-ATM, were assessed by western blotting. We used an NF-κB p65 transcription factor assay kit to evaluate NF-κB activity. We evaluated the antitumor effect of the combination of RT and ribociclib through the MCF-7 orthotopic xenograft model. The synergistic effects of combining RT with ribociclib and palbociclib pretreatment were demonstrated by clonogenic assay. CDK4/6 inhibitors synergistically increased the numbers of RT-induced γH2AX and 53BP1, downregulated the expression of p-DNA-PKcs, Rad51 and p-ATM activated by RT, and reduced RT-triggering p-ERK expression, NF-κB activation, and its down-streaming gene, c-Myc. Combined ribociclib and RT reduced the growth of MCF-7 cell xenograft tumors, and downregulated the immunohistochemical expression of p-ERK, p-NF-κB p65, and c-Myc compared to that in the control group. Combining CDK4/6 inhibitors enhanced radiosensitivity of HR-positive and HER2-negative breast cancer cells at least by reducing DNA-DSB repair and weakening the activation of ERK and NF-κB signaling by RT.

Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor–Positive Breast Cancer

Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking. To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer. This prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])-high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022. Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses. Tumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively. In this prospective-retrospective translational study of patients enrolled in SOFT, BCI was confirmed as prognostic in premenopausal women with HR+ breast cancer. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.

AI-based big data analysis of user-generated content to understand adherence in oral hormone receptor-positive advanced breast cancer treatment: A literature review and patient-centered approach using natural language processing

AI-based big data analysis of user-generated content to understand adherence in oral hormone receptor-positive advanced breast cancer treatment: A literature review and patient-centered approach using natural language processing

Endocrine therapy for early breast cancer in the era of oral selective estrogen receptor degraders: challenges and future perspectives.

Growth and survival of hormone receptor positive breast cancer cells are dependent on circulating hormones (e.g., estrogen and progesterone). Endocrine therapy improved outcomes in both early and advanced hormone receptor positive breast cancer. These treatments include drugs with different mechanisms of action, namely selective estrogen receptor modulators (SERM), aromatase inhibitors, and selective estrogen receptor degraders (SERDs). SERDs represent estrogen receptor antagonists, favoring its degradation and thus interfering with proliferation genes transcription and activation. Fulvestrant is the first approved SERD, administered intramuscularly for treating advanced breast cancer. Oral SERDs have been tested to overcome the limitation of the intramuscular administration, and to increase SERD bioavailability. Recently, an oral SERD, Elacestrant, has been approved by the Food and Drug Administration (FDA) for patients carrying an ESR1 mutation. In fact, oral SERDs seem to be effective in tumors harboring ESR1 mutations, a well known mechanism of resistance to endocrine therapy (especially aromatase inhibitors). More recently, oral SERDs have been tested in patients with early hormone receptor positive breast cancer, although their impact on survival and in this curative setting compared to standard endocrine therapy still needs to be elucidated. The best timing and duration of SERD administration and specific biomarkers in (neo)adjuvant setting remain largely unknown.

Reviewing the recurrence rates in stage I-III HR or ER positive breast cancer in obese patients given multi-modal weight loss plan post-treatment with aromatase inhibitors.

15 Background: Aromatase inhibitors (AIs) in the treatment of endocrine recepter positive breast cancer stages I-III, poses significant challenges in the management of obesity. Obesity is not only associated with an increased risk of breast cancer incidence but also with higher rates of cancer recurrence and poorer treatment outcomes. Moreover, the use of AIs, while effective in reducing estrogen levels and preventing ER or HR positive breast cancer recurrence, may exacerbate weight gain and metabolic disturbances in obese individuals. Weight management strategies have experienced increased attention in breast cancer survivors in recent years, especially overweight or obese individuals. Novel data makes it possible to infer that obesity management activities and multimodal programs that incorporate dietary counseling and physical activity can reduce recurrence rates. Methods: Participants in this study were individuals with Stage I-III endocrine receptor positive breast cancer who had completed adjuvant therapy and had a BMI in the 40s or 50s, increasing risk of recurrence. Eligible patients were identified based on the start date for endocrine therapy. High-risk patients were then assigned to either the intervention or control group. Those in the intervention group received access to a dietician, along with informational pamphlets on physiology and weight loss strategies. Additionally, they were offered discounts to certain gyms or provided free access to fitness facilities. Both intervention and control groups were briefed about the study, with those in the intervention group encouraged to utilize the provided resources for weight management. Results: The evidence from our study will underscore the potential benefits of multimodal weight loss interventions in overweight or obese breast cancer survivors, particularly in improving anthropometric outcomes and enhancing overall quality of life. Conclusions: While the studies included in our analysis demonstrated reductions in body weight, BMI, and waist circumference, as well as improvements in quality of life measures, there remains a notable gap in understanding the impact of these interventions on breast cancer recurrence rates, especially in the context of endocrine-positive breast cancer treated with Aromatase Inhibitors (AIs).

Therapeutic response and outcomes with uncommon breast cancer subtypes in the I-SPY trial 2010-2022.

1 Background: Uncommon histologies are over-represented among high-risk breast cancer (BC) and denote an area with limited trial data and of significant unmet medical need. To better understand trial outcomes in this group and identify signals of tumor responsiveness, we report pathologic complete response (pCR) and early event-free survival (EFS) by disease subtype in the I-SPY2 trial. Additionally, the I-SPY2 trial currently utilizes a combination of tumor molecular signature and receptor status to determine response predictive subtype (RPS) first developed from 987 I-SPY2 patients [Wolf et al, Cancer Cell 2022]. We report disease response rates for those who received what is now known to be optimal RPS guided therapy. Methods: The I-SPY2 platform trial tests novel agents given neo-adjuvantly with a chemotherapy backbone in high-risk BC (HER2 positive, triple negative and high molecular risk estrogen receptor positive BC). Histologic images of research biopsies, local biopsy and surgical pathology reports were reviewed centrally by I-SPY pathologists. Receptor subtype distribution and pCR rates were summarized; and EFS was estimated using the Kaplan Meier method. Association between pCR and EFS was evaluated using the Cox proportional hazard model with significance assessed by the log rank test. Results: 144/2118 (7%) of I-SPY2 participants were identified with metaplastic (60), lobular (55), mucinous (9), micropapillary (8), neuroendocrine (4) and other (8) BCS. Tumor receptor status, pCR rate and EFS by tumor type are shown in the Table. For the full cohort, pCR was associated with better EFS (hazard ratio (95% CI): 0.12 (0.02 - 0.88), p = 0.01). Within metaplastic (metapBC) 11/32 (34%) and 5/28 (18%) patients had a pCR with or without checkpoint blockade, respectively. By RPS group, 9 of 18 (50%) (13 metapBC, 3 other, 2 lobular) in the HER2-Immune+ group who received RPS optimized therapy had a pCR. In this group 6/13 (46%) with metapBC had a pCR. In the HER2+ driven RPS groups, pCR rate in the HER+HER2orBasal was 88% (7/8) and 0% (0/3) in the HER2+Luminal. Conclusions: High pCR rates observed in metapBC and other among subsets of often difficult to treat BC subtypes support novel approaches and provide a roadmap for future study of uncommon BCs. Outcomes were improved when therapy matched RPS vulnerabilities. Participants presenting with uncommon BC subtypes will be prospectively identified in the I-SPY2.2 trial to further develop effective approaches for this group. Clinical trial information: NCT01042379 .[Table: see text]

Cyclin-dependent kinase 4/6 inhibitors combined with stereotactic ablative radiotherapy in oligometastatic HR-positive/HER2-negative breast cancer patients.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have significantly improved the survival of patients with hormone receptor-positive HER2-negative advanced breast cancer (ABC). Although stereotactic ablative radiotherapy (SABR) is used more often in routine clinical practice, data on the safety and efficacy of combining SABR with CDK4/6i are lacking. Herein, we present the results of SABR combined with CDK4/6i in ABC. Patients with ABC who received CDK4/6i and SABR between 2018 and 2023 were analysed. Among 384 patients treated with CDK4/6i, 34 patients received 44 courses of SABR. Two-year progression-free survival (PFS) was 63.6% (95% CI, 45.8-88.3), and the median PFS was 32 months. Three-year overall survival (OS) was 88.9% (95% CI, 77.7-100). Two-year local control (LC) was 92.7% (95% CI, 83.4-100). Median OS and LC were not reached. The subgroup analysis showed the difference in survival between oligometastatic patients (OMD) and non-OMD subgroup. Two-year PFS was 69.2% (95% CI, 44.5-100) in OMD compared with 57.4% (95% CI, 36-91.7) in the non-OMD (P = .042). Three-year OS was 90% (95% CI, 73.2-100) in OMD compared with 86.2% (95% CI, 70-100) in the non-OMD (P = .67). Median PFS and OS in the non-OMD were 26 and 56 months, respectively, and were not reached in OMD. Fifteen patients required CDK4/6i dose reduction, and 2 discontinued treatment due to toxicity. No difference in high-grade toxicity was observed between the sequential and concurrent SABR. The addition of SABR to CDK4/6i seems to be safe and effective, especially in patients with oligometastatic disease. In advanced breast cancer patients treated with CDK4/6i, SABR provides a high local control and may provide additional benefit in an oligometastatic setting.

Triple Negative Evaluation of FFPE (Formalin Fixed Embedded Tissue) Breast Cancer Tissues in A Tertiary Health Institution of Bayelsa State, Nigeria

Breast cancer is a common disease worldwide, with over two million cases reported in 2018. Various therapy modalities use biological characteristics that influence treatment and outcomes to provide individualized care. Some biomarker advancements, such as hormone receptors, vascular endothelial growth factors, and HER2/neu receptors, have significantly contributed to the biological characterization of breast cancer. Triple-negative breast cancer is defined as malignancies that do not express hormone responsiveness or HER-2. Approximately 12% of women with breast cancer will have triple-negative illness, which is more common among non-Hispanic black women regardless of age, but is detected at a younger age than other subtypes. Women with triple-negative illness are more likely to be diagnosed at a later stage (stage III or IV). The pathogenesis of breast cancer is complex and poorly understood, however many risk factors are known. This cross-sectional study spanned from 2010 to 2022. In this study, the prevalence of triple-negative breast cancer in archived breast cancer cases at Federal Medical Centre Yenagoa, Bayelsa State, was analyzed using the Haematoxylin and Eosin Staining Technique on breast cancer samples collected over the study period. This study, done at Bayelsa State's Federal Medical Centre Yenagoa, analyzed 178 breast specimens. Ninety-six percent (96%) of the patients were IDC, and 5% were TNBC. The average age at presentation was 48.21 years, with 59.1% of patients being under 50 years. 40% of the patients exhibited HER-2/neu positive, and 65% had estrogen receptor (ER) positivity. The study was conducted in a single medical institution, and specific types of lesions were not included. Other potential limitations include comparing findings with various techniques and diagnostic protocols.

Monitoring of estradiol levels in premenopausal women receiving adjuvant abemaciclib and ovarian function suppression.

Approximately 15% of women who receive ovarian function suppression (OFS) as adjuvant treatment for high-risk, localized hormone receptor-positive (HR+) breast cancer may have inadequate estradiol suppression which can require therapeutic modification when used in combination with an aromatase inhibitor (AI). We previously reported that abemaciclib may interfere with the estradiol Abbott Alinity chemiluminescent microparticle immunoassay (CMIA) commonly used to monitor estradiol levels and suggested liquid chromatography-mass spectrometry (LC-MS/MS) is preferred in this setting. The aim of this study was to determine discrepancies in estradiol levels using CMIA compared to LC-MS/MS and subsequent treatment changes in a larger patient population. We conducted a retrospective review of premenopausal women with early-stage HR+ breast cancer at our institution who received adjuvant OFS and abemaciclib with at least 1 CMIA estradiol level drawn during abemaciclib therapy from October 2021 to April 2023. Of the 22 women who met criteria for review, 20 (90.9%) had CMIA estradiol levels in the premenopausal range, of whom 9 also had estradiol measured by LC-MS/MS. All 9 women receiving OFS and abemaciclib with estradiol measurements by both methods had premenopausal range CMIA estradiol levels and postmenopausal range LC-MS/MS estradiol levels. Of the 20 patients with premenopausal estradiol levels by CMIA estradiol, treatment changes included increased OFS dosage or preparation (n = 7), change from AI to tamoxifen (n = 3), and surgical oophorectomy (n = 7). Our findings suggest the likely interference of abemaciclib with the Abbott Alinity immunoassay which may lead to unnecessary treatment changes. It is recommended that the LC-MS/MS assay be used when monitoring estradiol levels in patients receiving abemaciclib concurrently with OFS.

The prognostic analysis of further axillary dissection in breast cancer with 1-2 positive sentinel lymph nodes undergoing mastectomy.

The ACOSOG Z0011 study has shown that axillary lymph node dissection (ALND) is an option to be considered in patients who had 1-2 metastatic sentinel lymph nodes (SLNs) who proceed with breast-conserving along with postoperative radiotherapy. However, there remains controversy regarding the applicability of this approach in patients who had a mastectomy. The aim of our study is to determine the prognostic differences and risk factors associated with the decision to opt for ALND in breast cancer patients who had 1-2 metastatic SLNs who receive a mastectomy. The study conducted a retrospective analysis of patients diagnosed with cT1-2N0 breast cancer and treated at The Fourth Hospital of Hebei Medical University between January 2016 and December 2021, and patients were divided into two cohorts according to whether ALND was performed after sentinel lymph node biopsy (SLNB): SLNB cohort and SLNB + ALND cohort. Outcomes included the locoregional recurrence rate (LRR), disease-free survival (DFS), and overall survival (OS). Propensity score matching (PSM) was conducted to ensure the balance of variables between the two cohorts. Cox proportional hazard models were employed to ascertain the univariate and multivariate relative risks associated with survival. There were 812 cases enrolled. After the PSM, 234 receiving ALND and 234 not receiving ALND were matched. A median follow-up period of 56.72 ± 20.29 months was observed. During that time, no significant difference was identified in the DFS and OS in the SLNB + ALND cohort and the SLNB cohort (P = 0.208 and P = 0.102), except for those under 40 years old, SLNB + ALND group showed a reduction in LRR compared to SLNB group (11.1% vs. 2.12%, P = 0.044). Multivariate Cox analysis showed that younger (≤ 40 years), progesterone receptor (PR)-negative, and SLNB alone were independent risk factors for LRR; perineural invasion was a risk factor, while endocrinotherapy was a beneficial prognostic indicator for DFS and OS among patients with positive hormone receptor. ALND does not impact DFS and OS in patients with 1-2 metastatic SLNs who have completed a mastectomy. Being younger (≤ 40 years), having a negative PR, and undergoing SLNB alone were independent risk factors for LRR. Given this finding, we recommend avoiding axillary treatment such as ALND or radiotherapy in patients without risk factors.

Confirming the efficacy and safety of CDK4/6 inhibitors in the first-line treatment of HR+ advanced breast cancer: a systematic review and meta-analysis.

Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods. Methods: Phase II or III randomized controlled trials in treatment-naive HR + patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes. Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (p = -1) and the first-order FP model (p = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR = 9.84, 95% CI: 8.13-11.95), especially for palbociclib (OR = 14.04, 95% CI: 10.52-18.90). Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR + advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively.

Accuracy of MRI Versus PET/CT in the Prediction of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer.

Background Breast-conserving surgeries have significantly advanced breast cancer treatment, offering favorable oncological outcomes, enhanced cosmetic results, reduced postoperative morbidity, and better psychological acceptance compared to mastectomy. The introduction of neoadjuvant therapy has expanded the applicability of breast conservation surgery to include locally advanced tumors. Tumor response to neoadjuvant chemotherapy is evaluated using imaging modalities such as breast ultrasound, breast magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). Accurate prediction of therapeutic response facilitates the planning of surgical and adjuvant treatments. This study aims to compare the diagnostic accuracy of MRI and PET/CT in predicting treatment response to neoadjuvant chemotherapy in breast cancer patients. Methods This retrospective study was conducted at a tertiary care center in Bahrain. A total of 138 patients with locally advanced breast cancer or human epidermal growth factor receptor-2 (HER2) positive, hormone receptor-negative cancers who underwent breast-conserving surgeries between June 2018 and December 2022 were included. The inclusion criteria focused on patients achieving a complete pathological responsefollowing neoadjuvant systemic therapy, ensuring a homogenous study population. Patients with hormone receptor-positive early breast cancers or metastatic tumors, ineligible for neoadjuvant chemotherapy, were excluded. Non-responders and partial responders were also excluded from the study. Statistical analysis was performed using IBM SPSS v26.0 (IBM Corp., Armonk, US). Response rates for the imaging modalities and histopathology results were assessed. Agreement between histology and imaging modalities was computed using kappa statistics. Diagnostic performance for predicting "no residual" disease was evaluated using the McNemar Test. All tests were two-tailed, with a p-value <0.05 considered statistically significant. Results The study included 138 patients, of whom 73 (52.9%) had an incomplete response or residual disease, while 65 (47.1%) had a complete response or no residual disease according to histology reports. There was slight agreement between post-neoadjuvant MRI and histology results (Cohen's kappa 0.172, p=0.010), while substantial agreement was observed between post-neoadjuvant PET/CT and histology results (Cohen's kappa 0.614, p=0.000). PET/CT demonstrated a higher sensitivity of 93.8% (p<0.001) and a specificity of 68.5%. Although MRI was more specific, the positive predictive value was comparable for both PET/CT and MRI. Conclusion PET/CT shows higher sensitivity and can serve as an early marker for predicting complete pathological response in post-neoadjuvant breast cancer patients. However, the prediction of residual disease is optimized by combining both MRI and PET/CT as diagnostic modalities.

Proton pump inhibitors decrease efficacy of palbociclib in patients with metastatic breast.

The objective of this investigation was to assess the impact of concurrent proton pump inhibitors (PPIs) on progression-free survival (PFS) in patients with hormone receptor-positive and HER2-negative metastatic breast cancer (mBC) who received palbociclib as first-line or successives therapy. A retrospective observational study was conducted, enrolling patients diagnosed with estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, and eligible for palbociclib treatment. Patients were categorized as "concurrent PPIs" if they received PPIs for at least two-thirds of the palbociclib therapy duration, and as "no concurrent PPIs" if they did not receive PPIs during the course of palbociclib treatment. A total of 165 patients were included in the study. Among first-line patients treated with palbociclib, those using concurrent PPIs exhibited a PFS of 8.88 months, while patients using palbociclib without concurrent PPIs had a PFS of 67.81 months (p < 0.0001). In second-line or subsequent treatments, patients on palbociclib with concurrent PPIs had a PFS of 7.46 months, whereas those using palbociclib without concurrent PPIs had a PFS of 17.29 months (p = 0.122). This study demonstrates that the concurrent use of PPIs in mBC patients receiving palbociclib negatively affects PFS, particularly in the first-line setting. Nevertheless, further investigation is warranted to explore the impact of PPIs on cycle-dependent kinase 4/6 inhibitors.

Populations of triple negative and hormone receptor positive HER2 negative breast tumors share immune gene profiles.

In breast cancer, triple negative (TN) breast cancer has most responses to immune checkpoint inhibitor (ICI) therapy. Lymphocyte infiltrate does not impact prognosis in Hormone receptor positive HER2 negative (HR + HER2-) breast tumors and few HR + HER2- tumors respond to ICI. We contrasted immune-associated gene expression between 119 TN and 475 HR + HER2- breast tumors from The Cancer Genome Atlas (TCGA) and confirmed our findings in 299 TN and 1369 HR + HER2- breast tumors in the METABRIC database. TN and HR+ HER2- tumors grouped into immune-high or -low tumors, both subtypes were represented in the immune-high group. The largest difference between the immune-high TN and HR + HER2- tumors was TN tumors had more abundant Th1 and Th2 CD4+ T cells while HR + HER2- tumors had more abundant fibroblasts (log2FC > 0.3; p < 10×10-10). This suggests an immune-high signature is not dictated by breast cancer subtype, but fibroblast subsets associated with worse outcome were higher in the immune-high HR + HER2- tumors.

Estrogen levels in young women with hormone receptor-positive breast cancer on ovarian function suppression therapy

Ovarian function suppression (OFS) benefits young women with hormone receptor (HR)-positive breast cancer but they are at risk for ovarian function breakthrough. We assessed endocrine effects of gonadotropin-releasing hormone agonist (GnRHa) treatment in a prospective cohort of patients aged ≤ 40 years with HR-positive breast cancer. Plasma estradiol (E2), estrone, and follicule-stimulating hormone (FSH) levels were measured from blood samples drawn 1 and 4 years after diagnosis. Patient characteristics, invasive breast cancer-free survival (iBCFS), and overall survival (OS) were compared between those with and without E2 > 2.72 pg/mL during GnRHa treatment. Among eligible patients, 54.7% (46/84) and 60% (15/25) had E2 > 2.72 pg/mL at 1 and 4 years, respectively. Factors associated with E2 > 2.72 pg/mL at 1 year were no prior chemotherapy (P = 0.045) and tamoxifen use (P = 0.009). After a median follow-up of 7 years, among patients with stage I-III breast cancer (N = 74), iBCFS events were seen in 6 (8.1%) with E2 > 2.72 pg/mL and 5 (6.8%) with E2 ≤ 2.72 pg/mL (P = 0.893). Among patients with de novo metastatic breast cancer (N = 12), 6 (50%) with E2 > 2.72 pg/mL and 3 (25%) with E2 ≤ 2.72 pg/mL died during follow-up (P = 0.052). Larger studies exploring the clinical implications of incomplete E2 suppression by GnRHa are needed to ensure optimal OFS treatment strategies are being employed for this population.

Adverse Event Profiles of the Third-Generation Aromatase Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS.

The third-generation aromatase inhibitors (AIs), represented by letrozole, anastrozole, and exemestane, have been used as a standard first-line adjuvant therapy for postmenopausal breast cancer patients with positive hormone receptor. However, their safety in the real world has not been systematically analyzed. We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate adverse event (AE) profiles of the three AIs, covering the period from Q1 2004 to Q3 2023. The time-to-event onset profiles and cumulative incidence were analyzed by Weibull shape parameter test and Kaplan-Meier method, respectively. The disproportionality analysis was utilized to assess drug toxicity risk. Based on the FAERS database, 18,035, 8242, and 7011 reports listing letrozole, anastrozole, and exemestane as primary suspected drugs were extracted, respectively. AEs associated with anastrozole displayed the latest onset (p < 0.0001); meanwhile, WSP test showed that all three AIs had early failure-type profiles. At the preferred term level, we acquired 95, 59, and 42 significant signals associated with letrozole, anastrozole, and exemestane, which involved 18, 13, and 15 system organ classes, respectively. The three AIs all reported that their strongest AE signal was trigger finger. Neutropenia was the most frequent AE for letrozole, while the highest occurrences of anastrozole and exemestane were arthralgia. We also found that interstitial lung disease, a rare but serious AE, showed strong signal intensity in all three AIs. Additionally, letrozole was also associated with lots of other rare but serious AEs in hematologic, respiratory, and hepatic systems, which were not recorded in the instructions. Our analysis of safety warning signals of the third-generation AIs from the FAERS database provided reference for clinical safe and rational drug use.

Trust in Black and White Breast Cancer Patients: Opportunities to Enhance Trustworthiness in Cancer Care

IntroductionThis study evaluated the relationships between patient and cancer delivery factors with trust in oncology providers in a racial/ethnically diverse group of cancer patients. MethodsData were analyzed from a prospective cohort study of women with hormone receptor positive (HR+) breast cancer. A standardized survey collected validated measures of trust in providers, psychosocial factors, and cancer care delivery factors. Multivariable logistic regression models and race-stratified models were employed to calculate odds ratios and 95% confidence intervals associated with trust. ResultsOf the 567 participants, 28% identified as Black and the rest were White. Compared to White women Black women reported lower trust in providers. Four domains of cancer care delivery were significantly associated with patients’ higher trust in their providers: general satisfaction with care (P < .0001), technical quality of the provider (P < .001), interpersonal manner of the provider (P = .0008) and provider communication (P = .0010). Race-stratified models revealed 2 significant cancer care delivery domains for both groups (ie, general satisfaction and interpersonal) and 2 care domains (technical quality and communication) that were only significant among White women. ConclusionEfforts are needed to nurture trusting relationships between Black women and their oncology providers. Factors related to the organization and delivery of cancer care are modifiable targets for interventions as these were robust predictors of patient trust regardless of a woman's self-reported race. Investments in strategies that strengthen the structure and organization of care towards a structures of trust worthiness may better support providers and patients and ultimately reduce cancer care disparities.

Factors Influencing Adherence to Adjuvant Endocrine Therapy After Breast Cancer Surgery.

Women with newly diagnosed hormone receptor-positive breast cancer are offered adjuvant endocrine therapy (AET). Despite the survival benefits of the therapy, a significant proportion of breast cancer patients do not adhere to the anti-hormonal medication. The purpose of this study was to analyse demographic, social, psychological and treatment-related factors influencing whether women diagnosed with early-stage breast cancer were adherent to offered therapy. This was a long-term retrospective, medical record study, supplemented with a questionnaire, including 81 women. Data from the Swedish Prescribed Drug Register were used to examine adherence. The women were followed for 5 years of offered AET. Out of 81 women, 67 (83%) were adherent (hade taken out 80% or more of the recommended dose), 10 (12%) were Partially Adherent and 4 (5%) never accepted AET. At baseline, the Never-Adherent group members were younger, more often considered themselves healthy and seemed much more satisfied with their lives. Baseline factors that positively affected adherence were satisfaction with the vocational situation (p = 0.023) and satisfaction with family life (p = 0.040). Cumulative musculoskeletal side effects were more frequently reported among women in the Adherent group than Partially Adherent women, after both 12 and 60 months (p = 0.018 and p = 0.011, respectively). There was also a significant difference in reported cumulative psychological side effects (p = 0.049) in disfavour of the Adherent group. Moreover, according to the questionnaire where the women retrospectively were asked which side effects, they experienced during the treatment period; sexual desire was significantly lower in the Adherent group (p = 0.0402) than in the Partially Adherent group. It is important to consider a woman's life situation, to support those who otherwise would not be able to complete AET and to help all women relieve side effects during AET. It should be investigated why some women did not start the recommended therapy.

Clinical and Biological Significance of HER2-Low in Ductal Carcinoma In Situ of the Breast

BackgroundDuctal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer, with 5-10% of cases progressing into invasive disease. Herein, we investigated the association between HER2-low and clinico-pathological characteristics in DCIS and subsequent ipsilateral loco-regional relapse (LRR). Materials and methodsWe accessed our prospectively maintained institutional database. HER2 status was determined by immunohistochemistry and classified as null (score 0), over-expressed (3+), and low (1+ or 2+); in situ hybridization was not considered since it is not used for routine DCIS diagnostics. ResultsAmong 375 patients with DCIS, median age was 54 (27-88) years, with a primary tumor size < 2.5 cm in 63%, grade III in 33%, and positive hormone receptor status (HR) in 81% of cases; 71% underwent breast-conserving surgery, 34% received adjuvant endocrine and 39% radiotherapy. A total of 197 (52%) had tumors with low HER2 expression, which resulted significantly associated with grade I/II (P < .001), Ki67< 20% (P < .001), and HR-positive status (P < .001). HER2-low distribution varied from 19.61% and 50% in ER negative and ER-low (<10%) to 60% and 69% in ER high (50%-95%) and very high tumors (> 95%) (P < .001). After a median 39-month follow-up (IQR 16-65), cumulative incidences of LRR was 0.054. Among 17 patients with paired primary tumor and LRR, 5 had discordant HER2 status, with an even distribution of increased and decreased HER2 expression. ConclusionsLow HER2 expression in DCIS is associated with features of reduced aggressiveness. Importantly, changes in HER2 expression may occur prompting retesting in recurrent cases, in line with observations in invasive breast cancer.