Clinicopathological and prognostic features of HER2-null and HER2-low advanced breast cancer treated with eribulin or capecitabine.

BACKGROUND: HER2-low populations constitute a heterogeneous group, and the cytotoxic anticancer agent efficacy based on HER2 status remains unclear. This study evaluated the clinicopathological features and outcomes of patients with advanced breast cancer showing HER2-low expression treated with eribulin or capecitabine, two treatment options after anthracycline and taxane treatment. METHODS: We retrospectively evaluated patients who were treated with eribulin or capecitabine between 2011 and 2015. HER2 status was evaluated according to the ASCO/CAP guidelines. RESULTS: No significant difference was observed in overall survival (OS; eribulin: hazard ratio [HR], 0.66; 95% CI 0.40-1.10; capecitabine: HR, 0.76; 95% CI 0.45-1.30) or progression-free survival (PFS; eribulin: HR, 1.13; 95% CI 0.72-1.78; capecitabine: HR, 0.90; 95% CI 0.56-1.44) between patients receiving eribulin (HER2-null: 35, HER2-low: 44) and those receiving capecitabine (HER2-null: 41, HER2-low: 33). Subgroup analysis revealed no significant differences in OS between the two groups in the hormone-positive and -negative populations for eribulin and capecitabine. HER2-null and HER2-low patients showed objective response rates (ORRs) of 22.5% and 9.1% (p = 0.09) overall, and 32.0% and 10.5% (p = 0.03), respectively, in hormone-positive cases among eribulin-treated patients. No response was observed in hormone-negative patients. Capecitabine treatment in HER2-null and HER2-low patients had overall ORRs of 26.8% and 15.2% (p = 0.23), respectively, with 27.3% and 16.1% (p = 0.28) for hormone-positive cases; and 25.0% and 0% (p = 1.0), respectively, for hormone-negative cases. CONCLUSIONS: Eribulin and capecitabine sensitivity may vary based on HER2 expression in patients with HER2-low and HER2-null breast cancer. Prognosis was similar between the HER2-low and the HER2-null groups.

Validity, reliability, responsiveness, and clinically meaningful change threshold estimates of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16).

BACKGROUND: Breast cancer is one of the most common cancers in women. Patient-reported outcome measures are used to evaluate patients' health-related quality of life in clinical breast cancer studies. This study evaluated the structure, validity, reliability, and responsiveness of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) subscales in a clinical trial featuring patients with advanced/metastatic breast cancer (aBC), and estimated NFBSI-16 meaningful change thresholds. METHODS: Data from 101 patients with aBC enrolled in a phase II trial (Xenera-1) were included for psychometric evaluation of the NFBSI-16. Subscale structure was evaluated by assessing inter-item correlations, item-total correlations, and internal consistency (cycles 2 and 5). Validity was assessed using scale-level convergent validity (cycles 2 and 5) and known-groups (Baseline). Reliability was analysed via test-retest at cycles 3-4, and responsiveness to improvement and worsening was evaluated at cycles 5, 7, and 9. Meaningful change thresholds were estimated using anchor-based methods (supported by distribution-based methods) at cycles 5, 7, and 9. RESULTS: NFBSI-16 internal consistency was acceptable, but item-total correlations suggested that its subscales and the GP5 item (side-effect of treatment) scores may be preferred over a total score. Convergent and known-groups evidence supported NFBSI-16 validity. Test-retest reliability was good to excellent for Total and DRS-P (disease-related symptoms: physical) scales, and moderate for the GP5 item. Responsiveness to worsening was generally demonstrated, but responsiveness to improvement could not be demonstrated due to limited observed improvement. Anchor-based meaningful change thresholds were estimated for DRS-P and Total scores. CONCLUSION: This study provides evidence that the NFBSI-16 has desirable psychometric properties for use in clinical studies in aBC. It also provides estimates of group- and individual-level meaningful change thresholds to facilitate score interpretation in future aBC research.

Assessment of Treatment Sequence in Patients With Stage III Breast Cancer.

INTRODUCTION: Stage III breast cancer is defined as locally advanced breast cancer and is treated with curative intent. Historically, overall survival (OS) did not differ based on treatment sequence (neoadjuvant chemotherapy [NAC] followed by surgery versus surgery followed by chemotherapy). Given recent advancements, we examined if treatment sequence may be associated with improved OS in a contemporary cohort of patients with stage III breast cancer. METHODS: Patients aged 18-80 years with prognostic stage III breast cancer who received chemotherapy and surgery were selected from the Surveillance, Epidemiology, and End Results database. Patients were stratified by treatment sequence (NAC versus surgery first). Unadjusted OS and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and compared with log-rank tests. Cox proportional hazards models were used to estimate the association of treatment sequence with OS and BCSS after adjustment for selected covariates. RESULTS: The study included 26,573 patients; median follow-up was 62.0 months (95% confidence interval [CI] 61.0-63.0). Patients receiving NAC had a worse OS and BCSS compared to those who underwent surgery first (5-year OS rates 0.66 versus 0.73; 5-year BCSS rates 0.70 versus 0.77; both log-rank P < 0.001). After adjustment for tumor subtype, receipt of NAC (versus surgery first) remained associated with a worse OS (hazard ratio 1.27, 95% CI 1.2-1.34, P < 0.001) and BCSS (hazard ratio 1.35, 95% CI 1.27-1.43, P < 0.001). CONCLUSIONS: Based on data from patients treated largely before 2020, undergoing surgery first may be associated with improved survival, even after adjustment for known covariates including tumor subtype. These findings may inform treatment when caring for patients with operable, locally advanced breast cancer.

Significance of phosphoinositide 3-kinase inhibitors in advanced breast cancer: a systematic review and meta-analysis.

BACKGROUND: The Phosphoinositide 3-kinase (PI3K) inhibitors may be used in cancer progression and mortality along with standard therapy to improve therapeutic efficacy of Advanced Breast Cancer (ABC). PURPOSE: This systematic review and meta- analysis were conducted to understand the therapeutic and toxicity profile of PI3K inhibitors in ABC. METHODS: The electronic databases were searched for suitable trials as per the criteria. The outcomes assessed were Progression- Free Survival, Objective Response Rate and Disease Control Rate. The data were systematically reviewed and meta-analyzed by Mantele- Haenszel method. RESULTS: Seven studies were included in the systematic review and meta- analysis. The co- administration of PI3K inhibitors with standard therapy improved the Progression- Free Survival significantly, while a marginal improvement was observed in Objective Response Rate, no difference in Disease Control Rate and toxicity significantly increased. CONCLUSIONS: The addition of PI3K inhibitors decreased the risk of progression but increased the risk of toxicity.

Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study.

PURPOSE: To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm). METHODS: OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile. RESULTS: A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4-99.5, p < 0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7-94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified. CONCLUSIONS: This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive gBRCAm ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for BRCA1/2-driven cancers.

Performance of Contrast-Enhanced Mammography (CEM) for Monitoring Neoadjuvant Chemotherapy Response among Different Breast Cancer Subtypes.

Neoadjuvant chemotherapy (NAT) plays a crucial role in breast cancer (BC) treatment, both in advanced BC and in early-stage BC, with different rates of pathological complete response (pCR) among the different BC molecular subtypes. Imaging monitoring is mandatory to evaluate the NAT efficacy. This study evaluates the diagnostic performance of Contrast-Enhanced Mammography (CEM) in BC patients undergoing NAT. This retrospective two-center study included 174 patients. The breast lesions were classified based on the molecular subtypes in hormone receptor (HR+)/HER2-, HER2+, and triple-negative breast cancer (TNBC). The histopathological analysis performed following surgery was used as a reference standard for the pCR. Sensitivity, specificity, PPV, and NPV were measured overall and for the different subtypes. We enrolled 174 patients, 79/174 (46%) HR+/HER2-, 59/174 (33.9%) HER2+, and 35/174 (20.1%) TNBC; the pCR was found in 64/174 (36.8%), of which 57.1% were TNBCs. In the total population, the CEM sensitivity and specificity were 66.2% and 75.2%, with a PPV of 61.4% and an NPV of 78.8%. The highest specificity (80.9%) and NPV (91.7%) were found in HR+/HER2-, while the highest sensitivity (70%) and PPV appeared (73.7%) in TNBC. The results indicate that CEM is a valid tool to assess the pCR, with different performances among the subtypes of BC.

Optimizing treatment sequence for inoperable locally advanced breast cancer: Long-term outcomes of surgery first versus neoadjuvant chemotherapy in a real-world setting.

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.

SGLT2 inhibition improves PI3Kα inhibitor-induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials.

PURPOSE: Alpelisib plus fulvestrant demonstrated a significant progression-free survival benefit versus fulvestrant in patients with PIK3CA-mutated HR+ /HER2- advanced breast cancer (ABC) (SOLAR-1). Hyperglycemia, an on-target adverse effect of PI3Kα inhibition, can lead to dose modifications, potentially impacting alpelisib efficacy. We report data from preclinical models and two clinical trials (SOLAR-1 and BYLieve) on Sodium glucose cotransporter 2 inhibitor (SGLT2i) use to improve PI3Kα inhibitor-associated hyperglycemia. METHODS: Healthy Brown Norway (BN), mild diabetic Zucker diabetic fatty (ZDF), and Rat1-myr-p110α/HBRX3077 tumor-bearing nude rats treated with alpelisib were analyzed for glucose and insulin control with metformin and dapagliflozin (SGLT2i) and alpelisib efficacy. Hyperglycemia adverse events (AEs) were compared between patients receiving SGLT2i with alpelisib (n = 19) and a propensity score-matched cohort not receiving SGLT2i (n = 74) in both trials. RESULTS: Dapagliflozin and metformin in BN and ZDF rats treated with alpelisib normalized blood glucose and reduced insulin levels. No signs of ketosis or drug-drug interaction were observed when metformin and dapagliflozin was administered with alpelisib. Alpelisib antitumor efficacy was maintained when used with dapagliflozin in tumor-bearing rats. Compared with a matched set of patients without SGLT2i, patients receiving SGLT2i had 4.9 and 6.4 times lower rates of grade ≥ 3 hyperglycemia AEs and hyperglycemia AEs resulting in alpelisib dose adjustments, interruptions, or withdrawals, respectively, and a relative reduction in risk of experiencing these AEs (70.6% and 35.7%). CONCLUSION: These data suggest adding an SGLT2i can effectively manage hyperglycemia, resulting in fewer alpelisib dose modifications and discontinuations in patients with PIK3CA-mutated HR+ /HER2- ABC (SOLAR-1: NCT02437318; BYLieve: NCT03056755).

Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer After Trastuzumab Failure (PROVE): A Prospective Phase 2 Study.

Purpose: Approximately 50-74% of patients with metastatic HER2-positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cut-off date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% CI: 8.3-18.5). With all patients evaluated, an ORR of 38.9% (95% CI: 23.1-56.5%) and a DCR of 83.3% (95% CI: 67.2-93.6%) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion: Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Elacestrant in the treatment landscape of ER-positive, HER2-negative, ESR1-mutated advanced breast cancer: a contemporary narrative review.

Introduction: Estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer with ESR1 mutations presents a significant therapeutic challenge due to its adaptive resistance mechanisms to chemotherapy, especially endocrine treatment. Elacestrant, a novel oral selective estrogen receptor degrader (SERD), has emerged as a promising agent in this treatment-resistant era. Method: A comprehensive search was conducted on pivotal clinical trials, including the RAD1901-005 Trial, EMERALD TRIAL, ELIPSE, and ELEVATE, focusing on their methodologies, patient populations, treatment regimens, and outcomes. Discussion: This narrative review describes the available preclinical and clinical evidence on elacestrant, focusing on its pharmacodynamics, pharmacokinetics, efficacy, and safety within the existing literature. Elacestrant has demonstrated excellent activity against ESR1 mutations associated with resistance to first-line endocrine therapies. Clinical trials have shown improved progression-free survival in patients with advanced ER+/HER2-, ESR1-mutated breast cancer. Safety profiles indicate a tolerable side effect spectrum consistent with other agents. Its oral bioavailability offers a convenient alternative to injectable SERDs, with potential implications for patient adherence and quality of life. The review also discusses the comparative efficacy of elacestrant relative to existing endocrine therapies and its possible use in combination regimens. Conclusion: Ongoing clinical trials assessing elacestrant and other SERDs will yield data that might aid clinicians in determining the optimal selection and order of endocrine treatment drugs for ER+ breast cancer. The integration of targeted and immunotherapeutic agents with traditional chemotherapy represents a pivotal shift in Breast Cancer treatment, moving towards more personalized and effective regimens.

Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer.

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell's subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2- mBC.

Multidisciplinary Treatment for Locally Advanced Mucinous Breast Cancer.

Background: Due to its indolent biology and high estrogen receptor positivity of mucinous breast cancer, vast majority of locally advanced mucinous breast cancer (LABC) are treated with first-line endocrine therapy. Case Presentation: A 50-year-old woman was referred to our hospital for the treatment of her huge breast tumor. Computed tomography showed an oval solid tumor, 17 cm in size, and lymph node swelling in both the axilla and parasternum. Pathological study of the core needle biopsy specimen showed the tumor to be luminal mucinous carcinoma. After the failure of endocrine therapy aiming for tumor regression, the patient received sequential chemotherapy to get favorable local control, leading to marked tumor shrinkage. Axillar and parasternal lymph nodes, however, remained unchanged in size. The patient further underwent mastectomy and regional lymph node dissection including removal of the still enlarged parasternal lymph nodes followed by covering of the large skin defect with the latissimus dorsi musculocutaneous (LDMC) flap using a spindle skin island, 15 × 8 cm in size. Postoperative pathological study showed sparse cancer cell remnants with abundant mucus in both the primary tumor and the dissected lymph nodes. The patient has been well without any recurrences on endocrine therapy for 21 months. Conclusion: Breast oncologists should note that multidisciplinary treatment including preoperative chemotherapy and skin defect covering using LDMC flap can give favorable local control even to breast cancer patients with LABC.

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.

Development and Validation of an Interpretable Machine Learning Prediction Model for Total Pathological Complete Response after Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: Multicenter Retrospective Analysis.

Objective: This study aims to develop an interpretable machine learning (ML) model to accurately predict the probability of achieving total pathological complete response (tpCR) in patients with locally advanced breast cancer (LABC) following neoadjuvant chemotherapy (NAC). Methods: This multi-center retrospective study included pre-NAC clinical pathology data from 698 LABC patients. Post-operative pathological outcomes divided patients into tpCR and non-tpCR groups. Data from 586 patients at Shanghai Ruijin Hospital were randomly assigned to a training set (80%) and a test set (20%). In comparison, data from our hospital's remaining 112 patients were used for external validation. Variable selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Predictive models were constructed using six ML algorithms: decision trees, K-nearest neighbors (KNN), support vector machine, light gradient boosting machine, and extreme gradient boosting. Model efficacy was assessed through various metrics, including receiver operating characteristic (ROC) curves, precision-recall (PR) curves, confusion matrices, calibration plots, and decision curve analysis (DCA). The best-performing model was selected by comparing the performance of different algorithms. Moreover, variable relevance was ranked using the SHapley Additive exPlanations (SHAP) technique to improve the interpretability of the model and solve the "black box" problem. Results: A total of 191 patients (32.59%) achieved tpCR following NAC. Through LASSO regression analysis, five variables were identified as predictive factors for model construction, including tumor size, Ki-67, molecular subtype, targeted therapy, and chemotherapy regimen. The KNN model outperformed the other five classifier algorithms, achieving area under the curve (AUC) values of 0.847 (95% CI: 0.809-0.883) in the training set, 0.763 (95% CI: 0.670-0.856) in the test set, and 0.665 (95% CI: 0.555-0.776) in the external validation set. DCA demonstrated that the KNN model yielded the highest net advantage through a wide range of threshold probabilities in both the training and test sets. Furthermore, the analysis of the KNN model utilizing SHAP technology demonstrated that targeted therapy is the most crucial factor in predicting tpCR. Conclusion: An ML prediction model using clinical and pathological data collected before NAC was developed and verified. This model accurately predicted the probability of achieving a tpCR in patients with LABC after receiving NAC. SHAP technology enhanced the interpretability of the model and assisted in clinical decision-making and therapy optimization.

Finding my tribe: a qualitative interview study of how people living with metastatic breast cancer perceive support groups.

PURPOSE: This study explored the value of metastatic breast cancer (MBC) support groups, and factors that affect attendance, from the perspective of people with MBC. METHODS: Semi-structured interviews were conducted with 28 women with MBC (support group attendees n = 16; non-attendees n = 12) between January 2022 and July 2023. Data were analysed using an inductive approach to thematic analysis. RESULTS: Three themes were generated: the value of sharing experiential knowledge, spaces for open and honest conversations, and opportunities to find connection and community. These factors were the main reasons that some participants valued, and chose to attend, an MBC support group. Stage-specificity and professional facilitation were identified as important aspects of group structure. Key reasons for non-attendance were concerns about misinformation, confronting the death of group members, and satisfaction with existing support networks. CONCLUSIONS: MBC support groups are beneficial for some people with MBC, providing opportunities to connect with others with the same diagnosis. For others, different forms of peer support such as online forums or one-on-one support may be preferred. We argue that ensuring those with MBC have equal access to the peer support they need will be essential in supporting people to live as well as possible with MBC. IMPLICATIONS FOR CANCER SURVIVORS: MBC support groups, if appropriately led, can provide emotional and informational benefits for people with MBC. This research may also have relevance to other metastatic cancers where novel therapies are extending survival, resulting in an emerging cancer population with distinct supportive and survivorship needs.

The treatment pattern of advanced HR-positive and HER2-negative breast cancer in central southern China: a hospital-based cross-sectional study.

AIMS: This investigation aims to elucidate the treatment status of advanced HR+/HER2- breast cancer patients in Hunan Province of Central Southern China from November 2021 to December 2022. METHODS: Data from 301 patients with advanced HR+/HER2- breast cancer were collected from the breast cancer investigation project in Hunan under the guidance of the Chinese Society of Clinical Oncolfogy (CSCO). The data included the clinical characteristics of patients and the status of first-line and second-line rescue treatment. RESULTS: First-line chemotherapy and endocrine therapy for mBC accounted for 40% (121/301) and 60% (180/301) of treatments, respectively. AI (21%), AI plus CDK4/6 inhibitor (28%), and fulvestrant (24%) or fulvestrant plus CDK4/6 inhibitor (18%) were the most common first-line endocrine therapies. Taxane-based chemotherapy was the most common first-line chemotherapy (59%). Second-line chemotherapy and endocrine therapy for mBC accounted for 43% (72/166) and 57% (94/166) of treatments, respectively. Fulvestrant (23%) or fulvestrant plus CDK4/6 inhibitor (29%) were the most common second-line endocrine therapies. The prevalences of AI and AI plus CDK4/6 inhibitor decreased to 19% and 11%, respectively. T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Third-line chemotherapy was more prevalent than endocrine therapy (57% vs. 41%). T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Fulvestrant plus CDK4/6 inhibitor was the most common endocrine therapy (33%). AI, AI plus CDK4/6 inhibitor, and fulvestrant accounted for 21%, 12% and 18% of third-line endocrine therapies, respectively. CONCLUSIONS: Compared to chemotherapy, endocrine therapy was a more favorable choice for first-line and second-line treatment for HR+/HER2- advanced breast cancer patients in Hunan Province.

The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer.

Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.Trial registration number: NCT05163106 (ClinicalTrials.gov).

[Box: see text].

Locoregional Radiotherapy in Patients with Advanced Breast Cancer Treated with Cyclin-Dependent Kinase 4/6 Inhibitors Based on Real-World Data.

BACKGROUND: The use of locoregional radiotherapy (RT) in patients with advanced ER-positive, HER2-negative breast cancer remains a topic of ongoing debate. In this study, we aimed to evaluate the efficacy of locoregional RT in advanced breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in a first-line setting. METHODS: We conducted a retrospective analysis of patients diagnosed with advanced breast cancer between 2018 and 2023 who received treatment with CDK4/6i and underwent locoregional radiotherapy. RESULTS: Among the 371 patients treated with CDK4/6i as part of their first-line therapy, 23 received locoregional RT either concurrently or sequentially with CDK4/6 inhibitors. Disease progression within the breast occurred in 19 patients (5.1%). Among these cases, five patients had previously undergone breast RT (5/23, 21.7%), while 14 did not (14/348, 4.0%, p = 0.004). All cases of local progression after RT followed palliative doses and were accompanied by early systemic progression. The 2-year PFS in the entire cohort of patients treated with locoregional RT was 65.7% (95% CI: 40.5-82.3%). Notably, patients who received higher RT doses had longer 2-year PFS (83.3%, 95% CI: 27.3-97.5%) than those with palliative RT doses (59.3%, 95% CI: 30.7-79.3%); however, the results were not statistically significant (p = 0.58). Furthermore, the 2-year local control in the entire cohort with locoregional RT was 73.0% (95% CI: 46.5-87.9%). Importantly, no local progression was observed after RT when using high doses. CONCLUSIONS: The addition of locoregional radiotherapy to first-line CDK4/6 inhibitors warrants further investigation across various clinical scenarios in advanced breast cancer. Palliative radiation regimens delivered early in breast oligoprogression may not always suffice, emphasizing the need for comprehensive studies in this context.

Long-Term Safety of Level II Oncoplastic Surgery after Neoadjuvant Treatment for Locally Advanced Breast Cancer: A 20-Year Experience.

Background: Oncoplastic surgery (OPS) reliability in the post-neoadjuvant chemotherapy (NACT) setting is still debated due to weak scientific evidences in such scenarios. Methods: Our analysis aims to report results obtained in a retrospective series of 111 patients consecutively treated with level II OPS after NACT at the Multidisciplinary Breast Center of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS between 1998 and 2018. The surgical endpoints were the mean specimen volume, rates of positive margins (PMR), re-excision (RR), conversion to mastectomy (CMR), and complications (CR). The oncological endpoints were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). To evaluate the impact of NACT on surgical and oncological outcomes at 302 months, we conducted a propensity score matching, pairing patients in post-NACT and upfront surgery groups. Results: The mean sample volume was 390,796 mm3. We registered a 3.6% of PMR, 1.8% RR, 0.9% CMR, 5% CR. The 10-year OS and 10-year DFS with a median follow-up of 88 months (6-302) were 79% and 76%, respectively, with an LR recurrence rate of 5%. The post-NACT group received significantly larger excised volumes and lower PMR. NACT did not affect surgical and oncological outcomes. Conclusions: Level II OPS can be considered a reliable alternative to mastectomy even in the post-NACT setting.

Serum lipid ratios as novel prognostic biomarkers for patients with locally advanced breast cancer treated with neoadjuvant therapy.

OBJECTIVES: To investigate the association between lipid ratios and survival outcomes in patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. METHOD: This retrospective study included patients with LABC receiving neoadjuvant chemotherapy. Serum lipid levels were prospectively measured at baseline. Associations of triglyceride to total cholesterol (TG/TC), triglyceride to high-density lipoprotein (TG/HDL) and triglyceride to low-density lipoprotein (TG/LDL) ratios with prognosis were evaluated. RESULTS: Patients with high TG/TC (adjusted hazard ratio [aHR] = 2.47, 95% CI: 1.10, 5.56, p = 0.029), TG/HDL (aHR = 2.73, 95% CI: 1.16, 6.41, p = 0.021) and TG/LDL (aHR = 2.50, 95% CI: 1.11, 5.65, p = 0.027) ratios were more likely to experience disease-free survival (DFS) events. Subgroup analysis suggested that the prognostic impact of lipid ratios was more pronounced in patients with negative HER2 status or those at a high risk of recurrence (e.g. clinical stage III, Ki67 > 30%). Additionally, higher lipid ratios tended to indicate early DFS events (0 ~ 2 years) (TG/TC p = 0.021, TG/HDL p = 0.046, TG/LDL p < 0.001), and the TG/LDL ratio demonstrated the best predictive efficacy (TG/TC vs. TG/HDL vs. TG/LDL, 1-year AUC: 0.724 vs. 0.676 vs. 0.846, 2-year AUC: 0.653 vs. 0.638 vs. 0.708). CONCLUSION: Baseline serum TG/TC, TG/HDL and TG/LDL ratios were independent prognostic factors in patients with LABC undergoing neoadjuvant therapy. However, their utility in predicting the early DFS events warrants further investigation. CLINICAL TRIAL REGISTRATION: NCT05621564.